We present a case of severe thyroid storm with simultaneous hypercalcemic crisis resulting from excessive intake of 5% Lugol’s iodine solution (5% iodine, 15% potassium iodide, 85% water; 10 drops/day) and vitamin D3 (10000 IU/day) during 2 months of unconventional treatment in a 78-year-old female with a history of hyperthyroidism in course of Graves’ disease. Supplements were prescribed by herbalist/healer before admission to the hospital. At the clinic, we started therapy with antithyroid drugs, inorganic iodide and corticosteroids but without positive effect. Patient’s condition kept deteriorating with loss of consciousness. Plasmapheresis (4 procedures) was required to successfully reduce thyroid hormone levels and finally total thyroidectomy was performed resulting in postoperative hypothyroidism and transient hypoparathyroidism. Additionally, patient suffered from serious complications such as Takotsubo cardiomyopathy and sepsis requiring intensive care unit. Treatment with corticosteroids led to secondary adrenal insufficiency. Following 2-month hospitalization, patient was discharged in stable condition.
{"title":"Thyroid storm and hypercalcemic crisis as a result of unconventional treatment of Graves’ disease","authors":"P. Miśkiewicz, M. Pelewicz-Sowa","doi":"10.20883/medical.e775","DOIUrl":"https://doi.org/10.20883/medical.e775","url":null,"abstract":"We present a case of severe thyroid storm with simultaneous hypercalcemic crisis resulting from excessive intake of 5% Lugol’s iodine solution (5% iodine, 15% potassium iodide, 85% water; 10 drops/day) and vitamin D3 (10000 IU/day) during 2 months of unconventional treatment in a 78-year-old female with a history of hyperthyroidism in course of Graves’ disease. Supplements were prescribed by herbalist/healer before admission to the hospital. At the clinic, we started therapy with antithyroid drugs, inorganic iodide and corticosteroids but without positive effect. Patient’s condition kept deteriorating with loss of consciousness. Plasmapheresis (4 procedures) was required to successfully reduce thyroid hormone levels and finally total thyroidectomy was performed resulting in postoperative hypothyroidism and transient hypoparathyroidism. Additionally, patient suffered from serious complications such as Takotsubo cardiomyopathy and sepsis requiring intensive care unit. Treatment with corticosteroids led to secondary adrenal insufficiency. Following 2-month hospitalization, patient was discharged in stable condition.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"119 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76222126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background. The clinical use of tamoxifen (TAM) may cause hepatotoxicity. Ursodeoxycholic acid (UDCA) has promising liver protective activity. This study assessed the protective effect of UDCA on TAM-induced hepatotoxicity in rats.Material and methods. Thirty five adult female Wistar rats were grouped into 7 of n=5/group. The rats were treated for 10 days as follows: Group 1: Water (10 mL/kg/day; placebo control) per oral [p.o], group 2: Ethanol 1% (1mL/kg/day; vehicle control) intraperitoneally (i.p), group 3: UDCA (40 mg/kg/day/p.o) and group 4: TAM (45 mg/kg/day) i.p. Groups 5-7 were pretreated with UDCA (10, 20 and 40 mg/kg), before daily treatment with TAM (45 mg/kg/day) i.p, respectively. On day 11, blood samples were collected and assessed for serum liver biomarkers. Liver samples were evaluated for oxidative stress markers and histology.Results. Significantly (p<0.05) decreased body weight and significantly (p<0.01) increased liver weight occurred in TAM- treated rats when compared to placebo control. TAM significantly (p<0.001) increased serum alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, aminotransferases, bilirubin, high density lipoprotein cholesterol levels and liver malondialdehyde levels when compared to control. TAM significantly (p<0.001) decreased liver glutathione, catalase, glutathione peroxidase, superoxide dismutase, serum total protein, albumin total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared to control. Steatosis and necrotic changes occurred in TAM-treated rats. UDCA pretreatment significantly prevents TAM-induced changes in serum biochemical markers, and oxidative stress indices in a dose-related fashion when compared to TAM. UDCA prevents TAM-induced changes in liver histology.Conclusion. UDCA may be clinically effective for TAM associated hepatotoxicity.
{"title":"Therapeutic benefit of ursodeoxycholic acid in tamoxifen-induced hepatotoxicity in Wistar rats","authors":"Elias Adikwu, B. Bokolo","doi":"10.20883/medical.e743","DOIUrl":"https://doi.org/10.20883/medical.e743","url":null,"abstract":"Background. The clinical use of tamoxifen (TAM) may cause hepatotoxicity. Ursodeoxycholic acid (UDCA) has promising liver protective activity. This study assessed the protective effect of UDCA on TAM-induced hepatotoxicity in rats.Material and methods. Thirty five adult female Wistar rats were grouped into 7 of n=5/group. The rats were treated for 10 days as follows: Group 1: Water (10 mL/kg/day; placebo control) per oral [p.o], group 2: Ethanol 1% (1mL/kg/day; vehicle control) intraperitoneally (i.p), group 3: UDCA (40 mg/kg/day/p.o) and group 4: TAM (45 mg/kg/day) i.p. Groups 5-7 were pretreated with UDCA (10, 20 and 40 mg/kg), before daily treatment with TAM (45 mg/kg/day) i.p, respectively. On day 11, blood samples were collected and assessed for serum liver biomarkers. Liver samples were evaluated for oxidative stress markers and histology.Results. Significantly (p<0.05) decreased body weight and significantly (p<0.01) increased liver weight occurred in TAM- treated rats when compared to placebo control. TAM significantly (p<0.001) increased serum alkaline phosphatase, lactate dehydrogenase, gamma-glutamyl transferase, aminotransferases, bilirubin, high density lipoprotein cholesterol levels and liver malondialdehyde levels when compared to control. TAM significantly (p<0.001) decreased liver glutathione, catalase, glutathione peroxidase, superoxide dismutase, serum total protein, albumin total cholesterol, low density lipoprotein cholesterol and triglyceride levels when compared to control. Steatosis and necrotic changes occurred in TAM-treated rats. UDCA pretreatment significantly prevents TAM-induced changes in serum biochemical markers, and oxidative stress indices in a dose-related fashion when compared to TAM. UDCA prevents TAM-induced changes in liver histology.Conclusion. UDCA may be clinically effective for TAM associated hepatotoxicity.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80616652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oluwaseyi Bamisaye, A. Fashina, F. Abdulraheem, O. Akanni, Fadiora S. Olufemi
Background. Studies have proven the effect of several agents, including natural products, to induce, prevent and treat genotoxicity through experimental models and clinical trials. In this study, the genotoxic preventive potential of Annona muricata ethanol extract on N-Ethyl-N-Nitrosourea (ENU)-induced pro-leukaemia in mice models using micronuclei formation in bone marrow was assessed. Materials and methods. Forty-eight mice weighing 18-24g were randomly divided into six groups of eight mice. The mice were intravenously administered 20mg/kg of NEU 48 hourly 3 times, 80mg/kg of NEU 48 hourly 3 times. The negative control was fed with feed and water only. We introduced 0.2ml (0.1g/ml) ethanolic extract of Annona muricata for 3 weeks prior to NEU low dosage administration, 0.2ml (0.1g/ml) ethanolic extract of Annona muricata for 3 weeks prior to ENU high dosage and Annona muricata (ethanolic extract) administration, and gave commercial diet to the adverse/ toxicity group. The bone marrow was harvested, smeared and stained using MayGrumwald. The procedure enabled the determination of micronucleus polychromatic erythrocytes (MNPCEs) microscopically. Results. Groups exposed to various dosages of the ENU yielded significantly increased MNPCEs, with group B producing higher MNPCEs. The groups treated with the extract displayed a significant reduction in the MNPCEs despite prior exposure to concentrations of NEU. The adverse group displayed no difference in MNPCEs compared with the negative control. Conclusion. The ENU induced genotoxicity depending on its concentration. The extract displayed a profound capacity to prevent genotoxicity and alleviate leukaemia with good tolerance.
背景。研究已经通过实验模型和临床试验证明了几种药物，包括天然产物，在诱导、预防和治疗遗传毒性方面的作用。在本研究中，通过在骨髓中形成微核，评估了番麻乙醇提取物对n -乙基- n -亚硝基脲(ENU)诱导的小鼠前白血病模型的遗传毒性预防潜力。材料和方法。48只体重18-24g的小鼠随机分为6组，每组8只。小鼠静脉注射NEU 20mg/kg 48小时3次，NEU 80mg/kg 48小时3次。阴性对照只饲喂饲料和水。在NEU低剂量给药前3周分别引入0.2ml (0.1g/ml)番麻醇提物，在ENU高剂量和番麻醇提物给药前3周分别引入0.2ml (0.1g/ml)番麻醇提物，并给予不良/毒性组商业饲粮。采集骨髓，用MayGrumwald涂片染色。该方法可在显微镜下测定微核多染红细胞(mnpce)。暴露于不同剂量ENU的组mnpce显著增加，其中B组mnpce更高。尽管先前暴露于NEU浓度，但用提取物处理的组mnpce显着降低。不良组mnpce与阴性对照组比较差异无统计学意义。ENU的遗传毒性取决于其浓度。提取物显示出深刻的能力，以防止遗传毒性和减轻白血病良好的耐受性。
{"title":"Genotoxic and chemopreventive potentials of ethanol leaves extract of Annona muricata on N-Ethyl-N-Nitrosourea-induced pro-leukaemia carcinogen in mice model by bone marrow micronucleus assay","authors":"Oluwaseyi Bamisaye, A. Fashina, F. Abdulraheem, O. Akanni, Fadiora S. Olufemi","doi":"10.20883/medical.e760","DOIUrl":"https://doi.org/10.20883/medical.e760","url":null,"abstract":"Background. Studies have proven the effect of several agents, including natural products, to induce, prevent and treat genotoxicity through experimental models and clinical trials. In this study, the genotoxic preventive potential of Annona muricata ethanol extract on N-Ethyl-N-Nitrosourea (ENU)-induced pro-leukaemia in mice models using micronuclei formation in bone marrow was assessed.\u0000Materials and methods. Forty-eight mice weighing 18-24g were randomly divided into six groups of eight mice. The mice were intravenously administered 20mg/kg of NEU 48 hourly 3 times, 80mg/kg of NEU 48 hourly 3 times. The negative control was fed with feed and water only. We introduced 0.2ml (0.1g/ml) ethanolic extract of Annona muricata for 3 weeks prior to NEU low dosage administration, 0.2ml (0.1g/ml) ethanolic extract of Annona muricata for 3 weeks prior to ENU high dosage and Annona muricata (ethanolic extract) administration, and gave commercial diet to the adverse/ toxicity group. The bone marrow was harvested, smeared and stained using MayGrumwald. The procedure enabled the determination of micronucleus polychromatic erythrocytes (MNPCEs) microscopically.\u0000Results. Groups exposed to various dosages of the ENU yielded significantly increased MNPCEs, with group B producing higher MNPCEs. The groups treated with the extract displayed a significant reduction in the MNPCEs despite prior exposure to concentrations of NEU. The adverse group displayed no difference in MNPCEs compared with the negative control.\u0000Conclusion. The ENU induced genotoxicity depending on its concentration. The extract displayed a profound capacity to prevent genotoxicity and alleviate leukaemia with good tolerance.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"2015 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87840676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haematopoietic stem cell graft derived from cord blood is standard therapy for several haematological malignancies and other diseases. The study reports cases of public and private (family) cord blood biobanking services and the related hematopoietic stem cell transplantation ever performed in Hong Kong. The published original research papers and review articles from inception to Nov 2022 have been searched for on Pubmed, Microsoft Academic Search, and Google Scholar to identify reports on existing or terminated cord blood biobanking and transplantation service in Hong Kong. Moreover, all data publicly available on the official websites of the local cord blood banks and local mainstream media has been analysed. The public Hong Kong Red Cross Blood Transfusion Service delivers the highest quantity of haematopoietic stem cell transplants. Among the private sector, HealthBaby releases the most cord blood units for clinical use in diseases in both autologous and allogeneic administration, followed by Cordlife HK. Both public and private (family) cord blood biobanks have been and continue to contribute to the Hong Kong cord blood donor registry. However, the growth of the cord blood inventory is detrimental to donor-recipient matching for lifesaving therapy.
{"title":"An overview of cord blood stem cell transplantation in Hong Kong","authors":"C. Leung","doi":"10.20883/medical.e741","DOIUrl":"https://doi.org/10.20883/medical.e741","url":null,"abstract":"Haematopoietic stem cell graft derived from cord blood is standard therapy for several haematological malignancies and other diseases. The study reports cases of public and private (family) cord blood biobanking services and the related hematopoietic stem cell transplantation ever performed in Hong Kong. The published original research papers and review articles from inception to Nov 2022 have been searched for on Pubmed, Microsoft Academic Search, and Google Scholar to identify reports on existing or terminated cord blood biobanking and transplantation service in Hong Kong. Moreover, all data publicly available on the official websites of the local cord blood banks and local mainstream media has been analysed. The public Hong Kong Red Cross Blood Transfusion Service delivers the highest quantity of haematopoietic stem cell transplants. Among the private sector, HealthBaby releases the most cord blood units for clinical use in diseases in both autologous and allogeneic administration, followed by Cordlife HK. Both public and private (family) cord blood biobanks have been and continue to contribute to the Hong Kong cord blood donor registry. However, the growth of the cord blood inventory is detrimental to donor-recipient matching for lifesaving therapy.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72584565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Symmetrical drug-related intertriginous and flexural exanthema (also known as Baboon syndrome) is a skin eruption in the intertriginous areas. It is believed to be a delayed-type hypersensitivity response to the drug which occurs secondary to systemic absorption of agents after cutaneous sensitization. Our case provides high quality clinical images to aid in clinical diagnosis of this uncommon skin eruption.
{"title":"A case of symmetrical drug-related intertriginous and flexural exanthema","authors":"S. Subhadarshani, A. Valluri","doi":"10.20883/medical.e742","DOIUrl":"https://doi.org/10.20883/medical.e742","url":null,"abstract":"Symmetrical drug-related intertriginous and flexural exanthema (also known as Baboon syndrome) is a skin eruption in the intertriginous areas. It is believed to be a delayed-type hypersensitivity response to the drug which occurs secondary to systemic absorption of agents after cutaneous sensitization. Our case provides high quality clinical images to aid in clinical diagnosis of this uncommon skin eruption.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"51 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89072967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Piotr Wlodarczyk, M. Witczak, A. Gajewska, Tomasz Chady, Igor Piotrowski
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease where both upper and lower motoneurons are damaged. Even though the pathogenesis of ALS is unclear, the TDP-43 aggregations and non-nuclear localization may be crucial to understanding this process. Despite intensive research on ALS therapies, only two lifespan-prolonging medications have been approved: Riluzole and Edaravone. Unravelling the TDP-43 pathology could help develop new ALS therapies using mechanisms such as inhibition of nuclear export, autophagy, chaperones, or antisense oligonucleotides. Selective inhibitors of nuclear export (SINEs) are drugs that block Exportin 1 (XPO1) and cause the accumulation of not exported molecules inside the nucleus. SINEs that target XPO1 are shown to slightly extend the survival of neurons and soften motor symptoms. Dysfunctional proteins, including TDP-43, can be eliminated through autophagocytosis, which is regulated by the mTOR kinase. Stimulating the elimination of protein deposits may be an effective ALS therapy. Antisense oligonucleotides (ASO) are single-stranded, synthetic oligonucleotides that can bind and modulate specific RNA: via ribonuclease H, inducing their degradation or inducing alternative splicing via blocking primary RNA transcripts. Current ASOs therapies used in ALS focus on SOD1, C9ORF72, FUS, and ATXN2, and they may be used to slow the ALS progression. Reversing the aggregation is a promising therapeutic strategy. Chaperones control other proteins' quality and protect them against stress factors. Due to the irreversible character of ALS, it is essential to understand its complicated pathology better and to seek new therapies.
{"title":"The role of TDP-43 protein in amyotrophic lateral sclerosis","authors":"Piotr Wlodarczyk, M. Witczak, A. Gajewska, Tomasz Chady, Igor Piotrowski","doi":"10.20883/medical.e710","DOIUrl":"https://doi.org/10.20883/medical.e710","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease where both upper and lower motoneurons are damaged. Even though the pathogenesis of ALS is unclear, the TDP-43 aggregations and non-nuclear localization may be crucial to understanding this process. Despite intensive research on ALS therapies, only two lifespan-prolonging medications have been approved: Riluzole and Edaravone. Unravelling the TDP-43 pathology could help develop new ALS therapies using mechanisms such as inhibition of nuclear export, autophagy, chaperones, or antisense oligonucleotides. Selective inhibitors of nuclear export (SINEs) are drugs that block Exportin 1 (XPO1) and cause the accumulation of not exported molecules inside the nucleus. SINEs that target XPO1 are shown to slightly extend the survival of neurons and soften motor symptoms. Dysfunctional proteins, including TDP-43, can be eliminated through autophagocytosis, which is regulated by the mTOR kinase. Stimulating the elimination of protein deposits may be an effective ALS therapy. Antisense oligonucleotides (ASO) are single-stranded, synthetic oligonucleotides that can bind and modulate specific RNA: via ribonuclease H, inducing their degradation or inducing alternative splicing via blocking primary RNA transcripts. Current ASOs therapies used in ALS focus on SOD1, C9ORF72, FUS, and ATXN2, and they may be used to slow the ALS progression. Reversing the aggregation is a promising therapeutic strategy. Chaperones control other proteins' quality and protect them against stress factors. Due to the irreversible character of ALS, it is essential to understand its complicated pathology better and to seek new therapies.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89764610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In the process of finding better therapeutics, thousands of new molecules are synthesised every day. Many of these can be poorly soluble in water, leading to a potentially promising drug being rejected during testing due to its poor solubility. Polyethylene glycol (PEG) has become known as an excellent modification to remedy this and was initially used to increase circulation time and reduce the immunogenicity of therapeutic proteins. Thus significantly increasing their safety and range of use. Another group of compounds in which significant benefits of pegylation have been seen are photosensitisers. Used in photodynamic therapy, they are often characterised by very high hydrophobicity. Pegylation of their structure significantly increases their affinity for cancer cells and facilitates their penetration through cell membranes. Classical small-molecule drugs can benefit from temporary combinations hydrolysed in the body or very short PEG chains. This approach allows a significant increase in the bioavailability of the drug while avoiding the disadvantages of small molecule pegylation. However, the most common motive for pegylation recently is the creation of drug carriers. Liposomes and nanoparticles make it possible to exploit the advantages of PEG to stabilise their structure and increase circulation time while not modifying the structure of the active compound. Unfortunately, PEGs also have their drawbacks. The first is their high molecular weight range, especially for longer chains, which poses difficulties in purification. Another is the emergence of antibodies directed against PEG. Nevertheless, pegylation is still an up-and-coming method for modifying pharmaceutically active molecules.
{"title":"Pegylation – in search of balance and enhanced bioavailability","authors":"Dawid Łażewski, M. Murias, M. Wierzchowski","doi":"10.20883/medical.e761","DOIUrl":"https://doi.org/10.20883/medical.e761","url":null,"abstract":"In the process of finding better therapeutics, thousands of new molecules are synthesised every day. Many of these can be poorly soluble in water, leading to a potentially promising drug being rejected during testing due to its poor solubility. Polyethylene glycol (PEG) has become known as an excellent modification to remedy this and was initially used to increase circulation time and reduce the immunogenicity of therapeutic proteins. Thus significantly increasing their safety and range of use. Another group of compounds in which significant benefits of pegylation have been seen are photosensitisers. Used in photodynamic therapy, they are often characterised by very high hydrophobicity. Pegylation of their structure significantly increases their affinity for cancer cells and facilitates their penetration through cell membranes. Classical small-molecule drugs can benefit from temporary combinations hydrolysed in the body or very short PEG chains. This approach allows a significant increase in the bioavailability of the drug while avoiding the disadvantages of small molecule pegylation. However, the most common motive for pegylation recently is the creation of drug carriers. Liposomes and nanoparticles make it possible to exploit the advantages of PEG to stabilise their structure and increase circulation time while not modifying the structure of the active compound. Unfortunately, PEGs also have their drawbacks. The first is their high molecular weight range, especially for longer chains, which poses difficulties in purification. Another is the emergence of antibodies directed against PEG. Nevertheless, pegylation is still an up-and-coming method for modifying pharmaceutically active molecules.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81356117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction. The use of traditional medicinal plant concoctions to cure or treat different diseases daily in African folk medicine. However, the effects of most medicinal plants on human health or genetic material remain unknown. This study thus aimed to evaluate the mutagenic and antimutagenic potentials of Asparagus laricinus Burch. cladodes, Senecio asperulus DC., and Gunnera perpensa L. roots extract in vitro. Methods. Neutral red uptake assay, alkaline comet assay, and the VITOTOX test was used with plant extract dilutions of 4, 20, 50, and 100 µg/ml, respectively, on hepatic (C3A) cells and Salmonella Typhimurium TA104 strains. Ethyl methane-sulfonate and 4-nitroquinoline oxide were used as positive controls for the comet and VITOTOX assays, respectively. Results. In vitro cytotoxicity and genotoxicity were not observed from all tested extracts, except for the two dichloromethane (DCM) extracts of S. asperulus and G. perpensa, which appeared to be cytotoxic with S9 metabolic activation, but not genotoxic or mutagenic. From the VITOTOX test results, none of the extracts appeared to have antimutagenic properties after treating S. Typhimurium strains with a known mutagen. Conclusions. These results confirm that previously reported anticarcinogenic properties of A. laricinus, S. asperulus, and G. perpensa did not result from the protective mechanism against genotoxicity but from other ones. Moreover, the negative mutagenic and cytotoxic activities of the tested plants highlighted the safe use of these medicinal plants in vitro. Therefore, S. asperulus and G. perpensa DCM extracts require further investigation for their possible in vivo cytotoxic effects on humans.
{"title":"Mutagenic and antimutagenic evaluation of Asparagus laricinus Burch., Senecio asperulus DC., and Gunnera perpensa L. to hepatic cells","authors":"P. Mfengwana","doi":"10.20883/medical.e745","DOIUrl":"https://doi.org/10.20883/medical.e745","url":null,"abstract":"Introduction. The use of traditional medicinal plant concoctions to cure or treat different diseases daily in African folk medicine. However, the effects of most medicinal plants on human health or genetic material remain unknown. This study thus aimed to evaluate the mutagenic and antimutagenic potentials of Asparagus laricinus Burch. cladodes, Senecio asperulus DC., and Gunnera perpensa L. roots extract in vitro.\u0000Methods. Neutral red uptake assay, alkaline comet assay, and the VITOTOX test was used with plant extract dilutions of 4, 20, 50, and 100 µg/ml, respectively, on hepatic (C3A) cells and Salmonella Typhimurium TA104 strains. Ethyl methane-sulfonate and 4-nitroquinoline oxide were used as positive controls for the comet and VITOTOX assays, respectively.\u0000Results. In vitro cytotoxicity and genotoxicity were not observed from all tested extracts, except for the two dichloromethane (DCM) extracts of S. asperulus and G. perpensa, which appeared to be cytotoxic with S9 metabolic activation, but not genotoxic or mutagenic. From the VITOTOX test results, none of the extracts appeared to have antimutagenic properties after treating S. Typhimurium strains with a known mutagen.\u0000Conclusions. These results confirm that previously reported anticarcinogenic properties of A. laricinus, S. asperulus, and G. perpensa did not result from the protective mechanism against genotoxicity but from other ones. Moreover, the negative mutagenic and cytotoxic activities of the tested plants highlighted the safe use of these medicinal plants in vitro. Therefore, S. asperulus and G. perpensa DCM extracts require further investigation for their possible in vivo cytotoxic effects on humans.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"87 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85210269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background. The principle of photodynamic effect is based on the combined action of photosensitiser, molecular oxygen and light, which produce various reactive oxygen species and are associated with significant cellular damage. Singlet oxygen is one of the most serious representatives, which is characterised by powerful oxidising properties. Moreover, concomitant hyperbaric oxygen treatment can support these effects. Therefore, the subject of our study was to compare the yields of singlet oxygen for four different photosensitizers in dependency on the oxygen concentration. Material and methods. Four different photosensitizers 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate), tetramethylthionine chloride, 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin zinc(II) and zinc phthalocyanine disulfonate were investigated to determine the yield of singlet oxygen in PBS by Singlet Oxygen Sensor Green reagent under different partial pressures of oxygen (0.4 and 36 mg/l). Results. There were no noticeable shifts in the excitation and emission fluorescence spectra regarding the oxygen concentration. Concerning the same molar concentration of photosensitizers the production of singlet oxygen was highest for 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin zinc(II), where the rate of the fluorescence change was more than 3 times higher than that obtained for 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate). On the other hand, zinc phthalocyanine disulfonate showed the lowest yield in singlet oxygen production. Conclusions. Singlet oxygen production, within the range of oxygen concentrations achievable in tissues under normoxia or hyperoxia, does not depend on these concentrations. However, the singlet oxygen generation is significantly influenced by the type of photosensitizer, with the highest yield belonging to 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin zinc(II).
{"title":"Generation of singlet oxygen by porphyrin and phthalocyanine derivatives regarding the oxygen level","authors":"M. Pola, H. Kolářová, R. Bajgar","doi":"10.20883/medical.e752","DOIUrl":"https://doi.org/10.20883/medical.e752","url":null,"abstract":"Background. The principle of photodynamic effect is based on the combined action of photosensitiser, molecular oxygen and light, which produce various reactive oxygen species and are associated with significant cellular damage. Singlet oxygen is one of the most serious representatives, which is characterised by powerful oxidising properties. Moreover, concomitant hyperbaric oxygen treatment can support these effects. Therefore, the subject of our study was to compare the yields of singlet oxygen for four different photosensitizers in dependency on the oxygen concentration.\u0000Material and methods. Four different photosensitizers 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate), tetramethylthionine chloride, 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin zinc(II) and zinc phthalocyanine disulfonate were investigated to determine the yield of singlet oxygen in PBS by Singlet Oxygen Sensor Green reagent under different partial pressures of oxygen (0.4 and 36 mg/l).\u0000Results. There were no noticeable shifts in the excitation and emission fluorescence spectra regarding the oxygen concentration. Concerning the same molar concentration of photosensitizers the production of singlet oxygen was highest for 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin zinc(II), where the rate of the fluorescence change was more than 3 times higher than that obtained for 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin tetra(p-toluenesulfonate). On the other hand, zinc phthalocyanine disulfonate showed the lowest yield in singlet oxygen production.\u0000Conclusions. Singlet oxygen production, within the range of oxygen concentrations achievable in tissues under normoxia or hyperoxia, does not depend on these concentrations. However, the singlet oxygen generation is significantly influenced by the type of photosensitizer, with the highest yield belonging to 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin zinc(II).","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"67 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83951385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human monkeypox represents a relatively underexplored infection that has received increased attention since the reported outbreak in May 2022. Due to its clinical similarities with human smallpox, this virus represents a potentially tremendous health problem demanding further research in the context of host-pathogen interactions and vaccine development. Furthermore, the cross-continental spread of monkeypox has reaffirmed the need for devoting attention to human poxviruses in general, as they represent potential bioterrorism agents. Currently, smallpox vaccines are utilized in immunization efforts against monkeypox, an unsurprising fact considering their genomic and phenotypic similarities. Though it offers long-lasting protection against smallpox, its protective effects against human monkeypox continue to be explored, with encouraging results. Taking this into account, this works aims at utilizing in silico tools to identify potent peptide-based epitopes stemming from the variola virus and monkeypox virus proteomes, to devise a vaccine that would offer significant protection against smallpox and monkeypox. In theory, a vaccine that offers cross-protection against variola and monkeypox would also protect against related viruses, at least in severe clinical manifestation. Herein, we introduce a novel multi-epitope mRNA vaccine design that exploits these two viral proteomes to elicit long-lasting humoral and cellular immunity. Special consideration was taken in ensuring that the vaccine candidate elicits a Th1 immune response, correlated with protection against clinically severe disease for both viruses. Immune system simulations and physicochemical and safety analyses characterize our vaccine candidate as antigenically potent, safe, and overall stable. The protein product displays high binding affinity towards relevant immune receptors. Furthermore, the vaccine candidate is to elicit a protective, humoral and Th1-dominated cellular immune response that lasts over five years. Lastly, we build a case about the rapidity and convenience of circumventing the live attenuated vaccine platform using mRNA vaccine technology.
{"title":"Multi-epitope mRNA Vaccine Design that Exploits Variola Virus and Monkeypox Virus Proteins for Elicitation of Long-lasting Humoral and Cellular Protection Against Severe Disease","authors":"Dženan Kovačić, Adnan Salihovic","doi":"10.20883/medical.e750","DOIUrl":"https://doi.org/10.20883/medical.e750","url":null,"abstract":"Human monkeypox represents a relatively underexplored infection that has received increased attention since the reported outbreak in May 2022. Due to its clinical similarities with human smallpox, this virus represents a potentially tremendous health problem demanding further research in the context of host-pathogen interactions and vaccine development. Furthermore, the cross-continental spread of monkeypox has reaffirmed the need for devoting attention to human poxviruses in general, as they represent potential bioterrorism agents. Currently, smallpox vaccines are utilized in immunization efforts against monkeypox, an unsurprising fact considering their genomic and phenotypic similarities. Though it offers long-lasting protection against smallpox, its protective effects against human monkeypox continue to be explored, with encouraging results. Taking this into account, this works aims at utilizing in silico tools to identify potent peptide-based epitopes stemming from the variola virus and monkeypox virus proteomes, to devise a vaccine that would offer significant protection against smallpox and monkeypox. In theory, a vaccine that offers cross-protection against variola and monkeypox would also protect against related viruses, at least in severe clinical manifestation. Herein, we introduce a novel multi-epitope mRNA vaccine design that exploits these two viral proteomes to elicit long-lasting humoral and cellular immunity. Special consideration was taken in ensuring that the vaccine candidate elicits a Th1 immune response, correlated with protection against clinically severe disease for both viruses. Immune system simulations and physicochemical and safety analyses characterize our vaccine candidate as antigenically potent, safe, and overall stable. The protein product displays high binding affinity towards relevant immune receptors. Furthermore, the vaccine candidate is to elicit a protective, humoral and Th1-dominated cellular immune response that lasts over five years. Lastly, we build a case about the rapidity and convenience of circumventing the live attenuated vaccine platform using mRNA vaccine technology.","PeriodicalId":16350,"journal":{"name":"Journal of Medical Science","volume":"4 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72470058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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