Medicines (Basel, Switzerland)最新文献

Cancer cells are characterized by metabolic reprogramming, which enables their survival in of-ten inhospitable conditions. A very well-documented example that has gained attraction in re-cent years and is already considered a hallmark of transformed cells is the reprogramming of carbohydrate metabolism. Such a feature, in association with the differential expression of en-zymes involved in the biosynthesis of glycoconjugates, generically known as glycosyltransfer-ases, contributes to the expression of structurally atypical glycans when compared to those ex-pressed in healthy tissues. The latest studies have demonstrated that glycophenotypic alterations are capable of modulating multifactorial events essential for the development and/or progres-sion of the disease. Herein, we will address the importance of glycobiology in modern medi-cine, focusing on the ability of unusual/truncated O-linked glycans to modulate two complex and essential phenomena for cancer progression: the acquisition of the multidrug resistance (MDR) phenotype and the activation of molecular pathways associated with the epithelial-mesenchymal transition (EMT) process, an event deeply linked with cancer metastasis.

Background: Adverse effects of antiseizure medications (ASMs) remain one of the major causes of non-adherence. Cosmetic side effects (CSEs) are among the most commonly reported side effects of ASMs. In this context, alopecia is one of the CSEs that has a high intolerance rate leading to poor therapeutical compliance. Methods: We performed a literature review concerning alopecia as a secondary effect of ASMs. Results: There are 1656 individuals reported with ASM-induced alopecia. Valproate (983), lamotrigine (355), and carbamazepine (225) have been extensively reported. Other ASMs associated with alopecia were cenobamate (18), levetiracetam (14), topiramate (13), lacosamide (7), vigabatrin (6), phenobarbital (5), gabapentin (5), phenytoin (4), pregabalin (4), eslicarbazepine (3), brivaracetam (2), clobazam (2), perampanel (2), trimethadione (2), rufinamide (2), zonisamide (2), primidone (1), and tiagabine (1). There were no reports of oxcarbazepine and felbamate with drug-induced alopecia. Hair loss seen with ASMs was diffuse and non-scarring. Telogen effluvium was the most common cause of alopecia. A characteristic feature was the reversibility of alopecia after ASM dose adjustment. Conclusions: Alopecia should be considered one important adverse effect of ASMs. Patients reporting hair loss with ASM therapy should be further investigated, and specialist consultation is recommended.

Background: The rhizome of Languas galangal is traditionally used in Sri Lanka for the treatment of skin infections caused by fungi. The aim of the present study was to evaluate the antifungal activity of L. galangal rhizome and to develop a topical antifungal formulation from it. Methods: The dried, powdered rhizome of L. galangal was successively extracted with hexane, dichloromethane, ethyl acetate and methanol using Soxhlet extraction. The agar well diffusion method was used to assess the antifungal activity against Candida albicans and Aspergillus nger. The antifungal activities of the extracts were compared with clotrimazole as the positive control and dimethyl sulfoxide (DMSO) as the negative control. The most active hexane extract was used to prepare the cream. The antifungal activity of the formulated cream was tested. Results: The hexane extract of L. galangal rhizome powder was more effective on C. albicans and A. niger. The hexane extract of L. galangal showed the maximum zone of inhibition against C. albicans and A. niger (20.20 mm ± 0.46, 18.20 mm ± 0.46) compared to the other three extracts, while clotrimazole, which was used as a positive control, produced a larger zone of inhibition (36.10 mm ± 0.65) and dimethyl sulfoxide (DMSO), the negative control, did not produce inhibitory zones. Stability testing of the formulated cream showed a stable and good appearance. Conclusions: The cream developed using the hexane extract showed in vitro antifungal activity against C. albicans and A. niger. Further evaluations on shelf life, stability and safety are required.

Background: Fluoroquinolones (FQNs) are related to several central nervous system side effects. This review aims to evaluate the clinical-epidemiological profile, pathophysiological mechanisms, and management of FQNs-associated movement disorders (MDs).

Methods: Two reviewers identified and assessed relevant reports in six databases without language restriction between 1988 and 2022.

Results: A total of 45 reports containing 51 cases who developed MDs secondary to FQNs were reported. The MDs included 25 myoclonus, 13 dyskinesias, 7 dystonias, 2 cerebellar syndromes, 1 ataxia, 1 tic, and 2 undefined cases. The FQNs reported were ciprofloxacin, ofloxacin, gatifloxacin, moxifloxacin, levofloxacin, gemifloxacin, and pefloxacin. The mean and median age were 64.54 (SD: 15.45) and 67 years (range: 25-87 years). The predominant sex was male (54.16%). The mean and median time of MD onset were 6.02 (SD: 10.87) and 3 days (range: 1-68 days). The mean and median recovery time after MD treatment was 5.71 (SD: 9.01) and 3 days (range: 1-56 days). A complete recovery was achieved within one week of drug withdrawal in 80.95% of the patients. Overall, 95.83% of the individuals fully recovered after management.

Conclusions: Future cases need to describe the long-term follow-up of the individuals. Additionally, FQN-induced myoclonus should include electrodiagnostic studies.

Coronavirus disease-2019 (COVID-19) has had and will have impacts on public health and health system expenses. Indeed, not only it has led to high numbers of confirmed COVID-19 cases and hospitalizations, but its consequences will remain even after the end of the COVID-19 crisis. Therefore, therapeutic options are required to both tackle the COVID-19 crisis and manage its consequences during the post COVID-19 era. Secreted protein acidic and rich in cysteine (SPARC) is a biomolecule that is associated with various properties and functions that situate it as a candidate which may be used to prevent, treat and manage COVID-19 as well as the post-COVID-19-era health problems. This paper highlights how SPARC could be of such therapeutic use.

Introduction: Primary sclerosing cholangitis sets the scene for several pathologies of both the intrahepatic and the extrahepatic biliary tree. Surgical treatment, when needed, is almost unanimously summarized in the creation of a Roux-en-Y hepaticojejunostomy, a procedure with a relatively high associated failure rate. Presentation of case: A 70-year-old male, diagnosed with primary sclerosing cholangitis, was submitted to a Roux-en-Y hepaticojejunostomy due to a dominant stricture of the extrahepatic biliary tree. Recurrent episodes of acute cholangitis dictated a workup in the direction of a possible stenosis at the level of the anastomosis. The imaging studies were inconclusive while both the endoscopic and the transhepatic approach failed to assess the status of the anastomosis. A laparotomy, with the intent to revise a high suspicion for stenosis hepaticojejunostomy, was decided. Intraoperatively, a decision to assess the hepaticojejunostomy prior to the scheduled surgical revision, via endoscopy, was made. In this direction, an enterotomy was made on the short jejunal blind loop in order to gain luminal access and an endoscope was propelled through the enterotomy towards the biliary enteric anastomosis. Results: The inspection of the anastomosis under direct endoscopic vision showed no evidences of stenosis and averted an unnecessary, under these circumstances, revision of the anastomosis. Conclusions: The surgical revision of a Roux-en-Y hepaticojejunostomy is a highly demanding operation with an increased associated morbidity, and it should be reserved as the final resort in the treatment algorithm. An approach of utilizing surgery to facilitate the endoscopic assessment prior to proceeding to the surgical revision of the anastomosis appears justified.

Background: Breast cancer (BC) is the most common type of cancer in Ethiopia. The incidence of BC is also rising, but the exact figure is still poorly known. Therefore, this study was conducted to address the gap in epidemiological data on BC in southern and southwestern Ethiopia. Materials and Methods: This is a five-year (2015-2019) retrospective study. The demographic and clinicopathological data were collected from biopsy reports of different kinds of breast carcinomas in the pathology department of Jimma University Specialized Hospital and Hawassa University Specialized Referral Hospital. Histopathological grades and stages were conducted using Nottingham grading and TNM staging system, respectively. Collected data were entered and analyzed using SPSS Version-20 software. Results: The mean age of patients at diagnosis was 42.27 (SD = 13.57) years. The pathological stage of most BC patients was stage III, and most of them had tumor sizes greater than 5 cm. Most patients had moderately differentiated tumor grade, and mastectomy was the most common type of surgery at the time of diagnosis. Invasive ductal carcinoma was the most common histological type of BC, followed by invasive lobular carcinoma. Lymph node involvement was seen in 60.5% of cases. Lymph node involvement was associated with tumor size (χ² = 8.55, p = 0.033) and type of surgery (χ² = 39.69, p < 0.001). Conclusions: This study showed that BC patients in southern and southwestern Ethiopia displayed advanced pathological stages, relatively young age at diagnosis, and predominant invasive ductal carcinoma histological patterns.

Background: Cannabis use by physicians can be detrimental for them and their patients. We conducted a systematic review and meta-analysis on the prevalence of cannabis use by medical doctors (MDs)/students. Method: PubMed, Cochrane, Embase, PsycInfo and ScienceDirect were searched for studies reporting cannabis use in MDs/students. For each frequency of use (lifetime/past year/past month/daily), we stratified a random effect meta-analysis depending on specialties, education level, continents, and periods of time, which were further compared using meta-regressions. Results: We included 54 studies with a total of 42,936 MDs/students: 20,267 MDs, 20,063 medical students, and 1976 residents. Overall, 37% had used cannabis at least once over their lifetime, 14% over the past year, 8% over the past month and 1.1 per thousand (‱) had a daily use. Medical students had a greater cannabis use than MDs over their lifetime (38% vs. 35%, p < 0.001), the past year (24% vs. 5%, p < 0.001), and the past month (10% vs. 2%, p < 0.05), without significance for daily use (0.5% vs. 0.05%, NS). Insufficient data precluded comparisons among medical specialties. MDs/students from Asian countries seemed to have the lowest cannabis use: 16% over their lifetime, 10% in the past year, 1% in the past month, and 0.4% daily. Regarding periods of time, cannabis use seems to follow a U-shape, with a high use before 1990, followed by a decrease between 1990 and 2005, and a rebound after 2005. Younger and male MDs/students had the highest cannabis use. Conclusions: If more than a third of MDs tried cannabis at least once in their lifetime, this means its daily use is low but not uncommon (1.1‱). Medical students are the biggest cannabis users. Despite being common worldwide, cannabis use is predominant in the West, with a rebound since 2005 making salient those public health interventions during the early stage of medical studies.

Background: Quercetin, a polyphenolic flavonoid found in various plants and foods, is known to have antioxidant, antiviral and anticancer effects. Although quercetin is well known to exert anti-inflammatory and anti-allergic effects, the precise mechanisms by which quercetin favorably modifies the clinical status of allergic diseases, such as allergic rhinitis (AR), remain unclear. The present study examined whether quercetin could modulate the production of the endogenous anti-inflammatory molecule, Clara cell 10-kD protein (CC10), in vitro and in vivo. Methods: Human nasal epithelial cells (1 × 10⁵ cells/mL) were stimulated with 20 ng/mL of tumor necrosis factor-alpha (TNF) in the presence of quercetin for 24 h. CC10 levels in culture supernatants were examined by ELISA. Sprague Dawley rats were sensitised with toluene 2,4-diisocyanate (TDI) by intranasal instillation of 10% TDI in ethyl acetate at a volume of 5.0 μL once daily for five days. This sensitisation procedure was repeated after an interval of two days. The rats were treated with different dosages of quercetin once daily for five days starting on the 5th day following the second sensitization. Nasal allergy-like symptoms induced by the bilateral application of 5.0 μL of 10% TDI were assessed by counting sneezing and nasal-rubbing behaviours for 10 min immediately after the TDI nasal challenge. The levels of CC10 in nasal lavage fluids obtained 6 h after TDI nasal challenge were examined using ELISA. Results: The treatment of cells with low doses of quercetin (<2.5 μM) scarcely affected TNF-induced CC10 production from nasal epithelial cells. However, the ability of nasal epithelial cells to produce CC10 after TNF stimulation significantly increased on treatment with quercetin doses (>5.0 μM). The oral administration of quercetin (>25 mg/kg) for five days significantly increased the CC10 content in nasal lavage fluids and attenuated the nasal symptoms induced by the TDI nasal challenge. Conclusions: Quercetin inhibits AR development by increasing the ability of nasal epithelial cells to produce CC10.

Background: The rise in antibody titers against the novel coronavirus (SARS-CoV-2) and its duration are considered an important indicator for confirming the effect of a COVID-19 vaccine, and self-paid tests of antibody titer are conducted in many facilities nationwide. Methods: The relationship between the number of days after the second and third dose of vaccines, age, and antibody titer was determined from the medical records of general internal medicine clinics that conducted self-paid testing of the SARS-CoV-2 antibody titer using Elecsys Anti-SARS-CoV-2 S (Roche Diagnostics); the relationship between the number of days after two or more doses of vaccines and antibody titer was also determined. We also examined the antibody titers in cases of spontaneous infection with SARS-CoV-2 after two or more doses of the vaccine. Results: Log-transformed SARS-CoV-2 antibody titers measured within 1 month from the second or third dose of vaccine showed a negative correlation with age (p < 0.05). In addition, the log-transformed antibody titers also showed a negative correlation trend with the number of days after the second dose of vaccine (p = 0.055); however, there were no significant correlations between the log-transformed antibody titers and the number of days after the third dose of vaccine. The median antibody titer after the third vaccination was 18,300 U/mL, more than 10 times the median antibody titer after the second dose of vaccine, of 1185 U/mL. There were also some cases of infection after the third or fourth dose of vaccine, with antibody titers in the tens of thousands of U/ml after infection, but the patients still received further booster vaccinations after the infection. Conclusions: The antibody titers after the third vaccination did not attenuate after a short follow-up period of one month, while they tended to attenuate after the second vaccination. It is considered that many people in Japan received further booster vaccinations after spontaneous infection, even though they already had antibody titers in the tens of thousands of U/mL due to "hybrid immunity" after spontaneous infection following two or more doses of vaccine. The clinical significance of the booster vaccination in this population still needs to be thoroughly investigated and should be prioritized for those with low SARS-CoV-2 antibody titers.