Drug metabolism and personalized therapy最新文献

Objectives: Urinary tract infection (UTI) is one of the most frequent reasons for prescribing antibiotics. Escherichia coli implicated in 75-90 % cases of UTI is becoming increasingly resistant to antibiotics. Finding alternative therapeutic agent for this infection is critical, for which herbal drugs may be an option. In Unani medicine, urinary tract infection (Ṭa'diya Majra-i-Bawl) is treated with herbal drugs possessing Da'fe Ufoonat (antiseptic), Muhallilat (anti-inflammatory) and Mudirrat (diuretic) properties. Polyherbal formulations of such drugs are expected to be beneficial in treating Escherichia coli infection. The aim of the study was to assess the efficacy and safety of a Unani polyherbal formulation aimed to develop a safe and efficacious drug for the treatment of urinary tract infection (Ṭa'diya Majra-i-Bawl) caused by Escherichia coli.

Methods: This open-label, single armed clinical study was conducted on patients with clinical signs and symptoms of UTI and positive urine culture for E. coli. Patients were treated with the polyherbal formulation consisting of 50 % hydro-alcoholic extracts of Khar Khasak (Tribulus terrestris), Bhui Amla (Phyllanthus niruri), Kabab Cheeni (Piper cubeba), Beekh -i-Kasni (Cichorium intybus), Beekh-i-Karafs (Apium graveolens), Asl-us-Soos (Glycyrrhiza glabra), and Giloy (Tinospora cordifolia) in a dose of one capsule (500 mg) thrice a day orally with plain water for 42 days.

Results: Maximum (83 %) urine cultures turned out negative for E. coli after the completion of therapy.

Conclusions: Polyherbal Unani formulation was found to be very effective for the treatment of Urinary tract infection. Clinical and microbiological cure was achieved in maximum number of patients and drug was very well tolerated without any adverse/side effect.

Introduction: Testosterone, the primary male sex hormone, orchestrates various physiological processes including sex differentiation, development of male characteristics, sperm production, and fertility. Its synthesis primarily occurs in Leydig cells within the testes, with smaller contributions from the ovaries and adrenal glands, all derived from cholesterol. Current therapeutic use of testosterone is mainly confined to treating hypergonadotropic hypogonadism, with limited off-label usage for augmenting muscle growth.

Content: This review delves into numerous studies investigating testosterone's therapeutic potential across various medical conditions as depicted in the figure given below.

Summary: Of all the studies in this review, which show a positive therapeutic result by using testosterone, the most promising areas of potential usage of testosterone are anxiety and diabetes mellitus, followed by obesity and depression.

Outlook: By the medium if this study, we want to not only enlist the various potential therapeutic uses of testosterone, but also promote a optimal hormonal balance, which can lead to prevention and/or better treatment outcomes for the mentioned diseases.

Objectives: Ibuprofen, a widely used non-steroidal anti-inflammatory (NSAID) for managing pain and inflammation in pediatric patients, is metabolized by the CYP2C8 enzyme. Studies suggest that the CYP2C8*2, *3, and *4 variations of the CYP2C8 gene diminish ibuprofen metabolism, increasing the risk of adverse reactions. The aim of this study was to determine the frequency of the CYP2C8*2, *3, and *4 alleles and genotypes in a pediatric population attending the King Abdulaziz University dental clinic and compare our findings to those of other populations.

Methods: A cross-sectional study was conducted with 140 healthy Saudi children ages 6-12. Saliva samples were collected using Oragene™ DNA Sample Collection Kits and analyzed for polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: The study identified that CYP2C8*2 AA, AT, and TT genotypes occurred at frequencies of 87.86 %, 9.29 %, and 2.86 %, respectively. For CYP2C8*3, AA, AG, and GG genotypes were found in 87.14 , 8.75, and 4.29 % of subjects, respectively. The CYP2C8*4 allele was less frequent, with CC and CG genotypes at 97.86 % and 2.14 %, respectively, and the GG genotype was absent. Allele frequencies for CYP2C8*2, *3, and *4 were 7.5 %, 8.57 %, and 1.07 %, respectively.

Conclusions: Our findings reveal that the allelic frequencies for the CYP2C8 polymorphisms in the Saudi pediatric cohort are substantially elevated compared to those reported in other Asian populations. This suggests Saudis may experience more varied drug responses, especially for medications that undergo metabolism by the CYP2C8 enzyme, like ibuprofen.

Objectives: Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. The existing study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90 days, respectively under OECD-423 and -408 guidelines as well as GLP compliance.

Methods: In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90 days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90 days were also observed.

Results: In acute toxicity, the results revealed that LD₅₀ of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90 days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes.

Conclusions: The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

Objectives: Withania somnifera (WS) is a valuable medicinal plant that has been used against several ailments. The medicinal properties of WS are ascribed to existence of secondary metabolites which are in great demand in herbal nutraceutical industry. Despite well-known therapeutic effects of WS, it is necessary to assess preclinical toxicity of WS plant on rats and further explore its potential application against treatment of various disorders in humans. The existing study assessed oral acute and sub-chronic toxicities of WS root extract in Sprague Dawley (SD) rats (male and female) for 14 and 90 days, respectively under OECD-423 and -408 guidelines as well as GLP compliance.

Methods: In acute toxicity, rats of either sex were orally fed a dose of 2,000 mg/kg. In sub-chronic toxicity, animals were orally administered repeated doses of WS root extract at 250, 500, 1,000 mg/kg for 90 days with an additional 14-day recovery period. Two more groups (n=5 animals each) receiving vehicle and 1,000 mg/kg of WS root extract for 90 days were also observed.

Results: In acute toxicity, the results revealed that LD₅₀ of WS root extract in SD rats was higher than 2,000 mg/kg. In sub-chronic toxicity, oral administration of extract for 90 days showed no significant toxicological changes in rats. Haematological and serum chemistry markers were found within normal range. Terminal necropsy showed no gross or histopathological outcomes.

Conclusions: The no-observed-adverse-effect level (NOAEL) of WS root extract was 1,000 mg/kg body weight, and safe to use at this dose in rats.

Introduction: 3-Dimensional printing (3DP) is an additive manufacturing (AM) technique that is expanding quickly because of its low cost and excellent efficiency. The 3D printing industry grew by 19.5 % in 2021 in spite of the COVID-19 epidemic, and by 2026, the worldwide market is expected to be valued up to 37.2 billion US dollars.

Content: Science Direct, Scopus, MEDLINE, EMBASE, PubMed, DOAJ, and other academic databases provide evidence of the increased interest in 3DP technology and innovative drug delivery approaches in recent times.

Summary: In this review four main 3DP technologies that are appropriate for pharmaceutical applications: extrusion-based, powder-based, liquid-based, and sheet lamination-based systems are discussed. This study is focused on certain 3DP technologies that may be used to create dosage forms, pharmaceutical goods, and other items with broad regulatory acceptance and technological viability for use in commercial manufacturing. It also discusses pharmaceutical applications of 3DP in drug delivery and drug screening.

Outlook: The pharmaceutical sector has seen the prospect of 3D printing in risk assessment, medical personalisation, and the manufacture of complicated dose formulas at a reasonable cost. AM has great promise to revolutionise the manufacturing and use of medicines, especially in the field of personalized medicine. The need to understand more about the potential applications of 3DP in medical and pharmacological contexts has grown over time.

The current review of tea and its parts is focused on the antibacterial properties, considering the possible applications and modes of action against bacterial illnesses. It shows the backdrop of antibiotic resistance and the huge demand for antibacterial treatments out there. From the interactions with bacterial components, the theory presented that tea polyphenols are antibacterial and therefore would be a substitute or supplementary therapy to the usual antibiotics. The study highlighted the role of tea polyphenols as potential antibacterial compounds that may interact with various bacterial components and different polyphenolic compounds occurring in tea. Future research directions may be directed toward testing more plant-based sources for antibacterial properties, in vivo validation of the studies, and possible synergistic effects with classical antibiotics. By addressing the controversies and disagreements involved, the present understanding of the topic of tea's antibacterial properties and enable the entry of new ways for fighting microorganisms resistant to antibiotics. In conclusion, this review adds to the growing body of evidence regarding the antimicrobial properties of tea and emphasizes the need for further studies that will allow the full exploitation of its therapeutic potential for countering the rising problem of antibiotic resistance in healthcare.

Objectives: Diastolic dysfunction represents an important pathophysiological intermediate between hypertension and heart failure. In the last two decades, the prevalence of heart failure patients having normal or near normal ejection fraction (EF) has increased to around 60 %. It thus poses a great morbidity and mortality risk to the population. In view of present scenario of high prevalence, lack of evidence-based therapy, and limited clinical trials, this study aimed to evaluate how a Unani formulation affects the improvement of the left ventricular diastolic function.

Methods: This clinical trial was set up as a randomized, placebo-controlled study involving 35 participants, with 18 individuals in the test group and 17 in the control group. Test group received 3.5 g of a polyherbal Unani formulation in capsule form along with 35 mL of an extract of Borago officinalis L. (Arq-e-Gaozaban), divided into two doses after meals. Meanwhile, the control group received a placebo in the same manner over an eight-week period. Follow-ups were conducted every 15 days to assess both subjective and objective parameters in all participants.

Results: The test formulation shows significant improvement in dyspnea and diastolic function from baseline to the end of trial (p<0.05), slight improvement in palpitations (p>0.05) and highly significant improvement in easy fatigability (p=0.001) as compared to the control.

Conclusions: The present study shows the effectiveness of the test drug in enhancing the diastolic function of left ventricle and alleviating other symptoms associated with ventricular diastolic dysfunction. Nevertheless, additional research with longer follow-up durations is necessary to clarify its efficacy and establish optimal treatment approaches for ventricular diastolic dysfunction in Unani medicine.

Objectives: The antiepileptic phenytoin has a narrow therapeutic window, nonlinear pharmacokinetics, and can cross the placenta causing apathy and jitteriness in postpartum newborns. Further, the sudden decay of phenytoin concentration can cause withdrawal seizures. This work aimed to assess the brain toxic exposure to phenytoin in newborns after transplacental transfer using neonatal saliva-brain correlations.

Methods: The phenytoin dose that the newborn receives transplacentally at birth was estimated using verified physiologically based pharmacokinetic (PBPK) model simulations in third-trimester pregnancy (pregnancy T3). Such doses were used as an input to the newborn PBPK model to estimate the neonatal levels of phenytoin and their correlations in brain extracellular fluid (bECF), plasma, and saliva.

Results: The PBPK model-estimated neonatal plasma and bECF concentrations of phenytoin were below the necessary thresholds for anticonvulsant and toxic effects. The neonatal salivary thresholds for phenytoin anticonvulsant and toxic effects were estimated to be 1.3 and 2.5 mg/L, respectively using the plasma-saliva-bECF correlations established herein.

Conclusions: The salivary TDM of phenytoin can be a more convenient option for avoiding phenytoin brain toxicity in newborns of epileptic mothers. Still, the appropriateness of using the same adult values of phenytoin anticonvulsant and toxic effects for infants needs investigation.

Objectives: The prevalence of microsatellite instability (MSI) subtype among all colon cancers in India is about 30 %, approximately two times more than that of western population suggesting different molecular pathogeneses.

Methods: A NanoString analysis-based Pan cancer differential expression (DE) profile was determined in a primary cohort of early-stage CRC (tumor=10, normal=7), and correlated against MSI status. Using RT-PCR, tumor-specific DE genes were validated in another cohort of MSI-high CRC (n=15).

Results: Among the most differentially expressed genes, AXIN2, ETV4, and RNF43 were tumor cell-specific signals, while a set of genes including COL11A1, COMP, INHBA, SPP1, MMP3, TLR2, and others were immune cell-specific signals, that had a differential expression between MSI and MSS groups. When overlapped with The Cancer Genome Atlas (TCGA) studies using the Tumor immune estimation resource tool (TIMER), and protein-protein interaction analysis by STRING.db, these genes were segregated to representative tumor cells and immune cells. On validation, the tumor-specific gene signals were inversely associated with TLR4 expression.

Conclusions: The differential expression distribution of AXIN2, ETV4, and RNF43 among tumor and immune cells, suggests more than one pathological subset in the MSI-H subgroup of early-stage CRC in the Indian population.