There are many factors involved in the effectiveness and efficiency of psychiatric drug treatment. One of them is psychotropic drug metabolism, which takes place mostly in the liver through the P450 enzyme system. However, there are genotypic variants of this system’s enzymes that can directly affect both the efficacy and the onset of side effects of a given therapeutic regimen. These genotypic changes could partly explain the lack of efficacy of treatment in certain patients. We report the case of a patient diagnosed with bipolar type I disorder that presented multiple and frequent manic episodes in which the efficacy and tolerability of several pharmacological regimens with mood stabilizers and antipsychotics was scarce. The choice of medical treatment should be based on its efficacy and side effect profile. This decision can be made more accurately using the information provided by pharmacogenetic analysis. This case illustrates the importance of pharmacogenetic studies in clinical practice. The results of pharmacogenetic analysis helped to decide on a better treatment plan to achieve clinical improvement and reduce drug-induced adverse effects.
Antipsychotic Agents ; Bipolar Disorder ; Cytochrome P-450 Enzyme System ; Humans ; Liver ; Metabolism ; Pharmacogenetics ; Precision Medicine

The aim of this study was to evaluate the cicatricial repair of perforating cornea in rabbits, by using the Nbutyl cyanoacrylate adhesive compared to the 910-polyglactine thread suture through macroscopic and histological assays. Corneas from 18 adult rabbits were perforated and subsequently occluded with N-butyl cyanoacrylate synthetic adhesive (right cornea) or by separated single points using the 910-polyglactine thread (left cornea). The rabbits were divided into groups containing three animals per group. Examination after 7, 15, and 30 days post-operative showed that both the synthetic adhesive and the suture were efficient in the occlusion of the surgical wounds, thus stabilizing the intra-ocular content. The N-butyl cyanoacrylate adhesive was shown to be superior to the 910-polyglactine suture thread with regards to the evolution and the organization of the healing process.
Animals ; Cornea/*injuries/*surgery ; Enbucrilate/*therapeutic use ; Female ; Male ; Polyglactin 910/therapeutic use ; Rabbits/*surgery ; *Sutures ; Tissue Adhesives/*therapeutic use ; *Wound Healing

Background. Emergence of multidrug-resistant tuberculosis (MDR-TB) poses a major challenge to prevailing disease management. MDR-TB arises from mutations in several genes comprising the resistance determining regions, including rpoB, katG and gyrA. Objective. To detect and characterize mutations in rpoB, katG and gyrA. Methods. Thirty selected Mycobacterium tuberculosis isolates from the IDS-PGH were subjected to PCR amplification and sequencing. Sequences were compared to the wild type strain H37Rv. Results. Mutations were detected in codons 512, 513, 516, 522, 526, 531 and 533 of rpoB, codons 280, 281, 315 and 333 of katG, and codons 90 and 94 of gyrA sequences. The most frequently mutating codons for rpoB, katG and gyrA were 531, 315 and 94, respectively. A clustering analysis of the sequences showed occurrence of seven, four and three clusters for the genes rpoB, katG and gyrA, respectively. The eight clusters obtained from the concatenated sequences of the three genes represent the eight potential genotypes of local strains. One cluster represents the wild type strain genotype, another cluster represents the XDR strain genotype, and six clusters represent the MDR strain genotypes. Conclusion. These findings indicate the utility of multiple RDR sequence analysis in both identifying specific drug resistance mutation and genotyping of various M. tuberculosis isolates.
TUBERCULOSIS ; THERAPEUTICS ; THERAPY

Polyphenols are the secondary metabolic products of plants and are considered as active constituents to possess therapeutic effects. To date, a vast number of scientific literature addressed the potential of polyphenols as bio-efficient compounds owing to their structural diversity. Due to the presence of several hydroxyl groups, they are metabolized quickly due to conjugation reaction and thus, readily produce toxic metabolites as a defense material against many pathogens, reflecting their safety strategy. This review focuses on the anti-quorum sensing and biofilm inhibition activity of polyphenols, which display their potential to treat bacterial infections by combating the virulence caused by pathogenic agents. Thus, for mitigating quorum sensing-controlled pathogenesis, the use of polyphenol-based phytochemicals holds immense potential to cure infections. The application of polyphenol as sensitizing agent/ adjuvant therapeutics which act in synergism with antibiotics is highly remarkable.

Objective: To evaluate antioxidant, cytotoxic, and anti-venom capacity of crude bark extracts of Alstonia parvifolia Merr. Methods: Gas chromatography-mass spectrometry (GC-MS) and energy dispersive X-ray analyses were accomplished to characterize the chemical constituents of Alstonia parvifolia. Biochemical characterization was evaluated using an inhibitory phospholipase A 2 (PLA 2) assay, DPPH, and cytotoxicity assays. Using the constituents listed in the GC-MS analyses, molecular docking was conducted to inspect the binding energies between the chosen compounds and selected PLA 2 isoforms. Results: GC-MS analyses showed that the Alstonia parvifolia crude extract consisted predominantly of acetylmarinobufogenin (14.89%), γ-sitosterol (10.44%), 3-O-methyl-D-glucose (5.88%), 3,5-dimethoxy-4-hydroxyphenylacetic acid (5.30%), (2α,5α)-17-methoxyaspidofractinin-3-one (AFM) (4.08%), and 2,3,5,6,7,8,9-heptahydro-1-phenyl-5-(p-chlorophenylimino)-1H-benzo[e] [1],[4] thiazepine (HPT) (1.37%). The principal elemental components of Alstonia parvifolia were Ca (4.012%) and K (1.496%), as exhibited by energy dispersive X-ray examination. Alstonia parvifolia showed significant free radical scavenging ability (IC 50: 0.287 mg/mL) and was non-cytotoxic to normal HDFn cells (IC 50 >100 μg/mL). Moreover, Alstonia parvifolia was favorably cytotoxic to MCF-7 (IC 50: 4.42 μg/mL), followed by H69PR, HT-29, and THP-1, with IC 50 values of 4.94, 5.07, and 6.27 μg/mL, respectively. Alstonia parvifolia also displayed notable inhibition against PLA 2 activity of Naja philippinensis Taylor venom with IC 50 of (15.2 ± 1.8) μg/mL. Docking and cluster analyses projected negative binding energies from AFM (-6.36 to -9.68 kcal/mol), HPT (-7.38 to -9.77 kcal/ mol), and acetylmarinobufogenin (-7.22 to -9.59 kcal/mol). These calculations were for the particular interactions of Alstonia parvifolia constituents to PLA 2 homologues where the utmost affinity was detected in HPT owing to the dipole interactions with amino acid residues. Conclusions: The bark extract of Alstonia parvifolia shows great potential as an anti-venom agent due to its low cytotoxic profile, remarkable PLA 2 inhibition, and docking binding energies between its bioactive constituents and PLA 2 homologues.