Consanguineous marriages increase the incidence of recurrent tuberculosis: Evidence from whole exome sequencing.

BACKGROUND: In this study, we have identified multiple mutations in the IL-12R1 gene among Pakistani patients who have inherited them through consanguineous marriages. These patients have experienced severe Bacille-Calmette-Guérin (BCG) infection as well as recurrent tuberculosis. We will demonstrate the pivotal role of interleukin (IL)-12/interferon (IFN)-γ axis in the regulation of mycobacterial diseases. METHODOLOGY: First, we checked the patients' medical records, and then afterward, we assessed interferon-gamma (IFN-γ) production through ELISA. Following that, DNA was extracted to investigate IL-12/IFN- abnormalities. Whole exome sequencing was conducted through Sanger sequencing. Secretory cytokine levels were compared from healthy control of the same age groups and they were found to be considerably less in the disease cohort. To evaluate the probable functional impact of these alterations, an in silico study was performed. RESULTS: The study found that the patients' PBMCs produced considerably less IFN-γ than expected. Analysis using flow cytometry showed that activated T cells lacked surface expression of IL-12Rß1. Exon 7 of the IL-12Rß1 gene, which encodes a portion of the cytokine binding region (CBR), and exon 10, which encodes the fibronectin-type III (FNIII) domain, were found to have the mutations c.641 A > G; p.Q214R and c.1094 T > C; p.M365T, respectively. In silico analysis showed that these mutations likely to have a deleterious effect on protein function. CONCLUSION: Our findings indicate the significant contribution of the IL-12/IFN-γ is in combating infections due to mycobacterium. Among Pakistani patients born to consanguineous marriages, the identified mutations in the IL-12Rß-1 gene provide insights into the genetic basis of severe BCG infections and recurrent tuberculosis. The study highlights the potential utility of newborn screening in regions with mandatory BCG vaccination, enabling early detection and intervention for primary immunodeficiencies associated with mycobacterial infections. Moreover, the study suggests at the potential role of other related genes such as IL-23Rß1, TYK2, or JAK2 in IFN-γ production, warranting further investigation.

In Silico identification of novel phytochemicals that target SFRP4: An early biomarker of diabesity.

The simultaneous coexistence of complicated metabolic conditions like obesity and diabetes within an individual is known as diabesity. Obesity is the key factor for many chronic diseases, including insulin resistance and type 2 diabetes (T2D). Metabolic stress due to nutrient overload releases different inflammatory mediators. Secreted frizzled-related protein 4 (SFRP4) is also an inflammatory mediator that impairs insulin secretion. SFRP4 acts as an early biomarker for diabesity expressed with interleukin-1 beta (IL-1ß) in the adipose tissues that hinder the exocytosis of insulin-secreting granules from the pancreatic ß-cells and is a potential target for preserving ß-cell dysfunction and the diabesity treatment. The current study aimed to screen potential bioactive compounds targeting and inhibiting the diabesity-linked SFRP4 protein through an in silico approach. The three-dimensional (3D) structure of human SFRP4 was predicted through comparative modeling techniques and evaluated by various online bioinformatics tools. The molecular docking and MD simulation investigations were carried out against phytochemicals with anti-diabetic and anti-obesity properties to shortlist the best SFRP4 inhibitor. Hesperetin, Curcumin, Isorhamnetin, Embelin, Epicatechin, and Methyl Eugenol interacted strongly with SFRP4 by displaying zero RMSD and binding affinities of -6.5, -6.4, -6.3, -5.3, -6.3 and -5.8 kcal/mol respectively. Additionally, the root mean square fluctuation and root mean square deviation graphs from the MD simulation results demonstrated that hesperetin has good variations throughout the simulation period as compared to others. This dynamic stability and control behavior of hesperetin, when it interacts with SFRP4, shows that it has the potential to modulate the function and activity of the protein. Therefore, hesperetin is identified as an effective and top drug candidate through this analysis for preserving beta-cell function and treating diabesity by targeting SFRP4. The findings of this study could be useful in the design and development of diabesity drugs.

Bio-Oriented Synthesis and Molecular Docking Studies of 1,2,4-Triazole Based Derivatives as Potential Anti-Cancer Agents against HepG2 Cell Line.

Triazole-based acetamides serve as important scaffolds for various pharmacologically active drugs. In the present work, structural hybrids of 1,2,4-triazole and acetamides were furnished by chemically modifying 2-(4-isobutylphenyl) propanoic acid (1). Target compounds 7a-f were produced in considerable yields (70-76%) by coupling the triazole of compound 1 with different electrophiles under different reaction conditions. These triazole-coupled acetamide derivatives were verified by physiochemical and spectroscopic (HRMS, FTIR, 13CNMR, and 1HNMR,) methods. The anti-liver carcinoma effects of all of the derivatives against a HepG2 cell line were investigated. Compound 7f, with two methyl moieties at the ortho-position, exhibited the highest anti-proliferative activity among all of the compounds with an IC50 value of 16.782 µg/mL. 7f, the most effective anti-cancer molecule, also had a very low toxicity of 1.190.02%. Molecular docking demonstrates that all of the compounds, especially 7f, have exhibited excellent binding affinities of -176.749 kcal/mol and -170.066 kcal/mol to c-kit tyrosine kinase and protein kinase B, respectively. Compound 7f is recognized as the most suitable drug pharmacophore for the treatment of hepatocellular carcinoma.

Graphene oxide/chitosan composites as novel support to provide high yield and stable formulations of pectinase for industrial applications.

An extracellular pectinase from a mixed consortium of Bacillus sp. (BSP) was immobilized onto graphene oxide/chitosan composite (GO/CS) through covalent binding to enhance its recycling and operational stability features. Different parameters were optimized, including cross-linker concentration (%), time, pH, and GO/CS-pectinase ratios. GO/CS-pectinase was further characterized by FT-IR and XRD. The activity of GO/CS-pectinase was reached up to 804 µmolmin-1 with an immobilization efficiency of 80.64 ± 1.15 % under optimum conditions. GO/CS-pectinase exhibited a 3.0-folds higher half-life (t1/2) than free pectinase at 50, 55, and 60 °C, respectively. The Vmax and KM values of GO/CS-pectinase were found to be nearly equal to the free pectinase indicating that conformational flexibility was retained. Kd, t1/2, ∆G*, ∆H*, and ∆S* of both free pectinase and GO/CS-pectinase was 0.0339 & 0.0721 min-1, 9.62 and 40.44 min, 81.35, 90.72 kJmol-1, 47.098 & 63.635 kJmol-1, -102.86 & -81.340 Jmole-1 K-1. SEM morphological analysis further confirmed the successful binding of pectinase with GO/CS, which retained about 92 % of its original catalytic activity after ten consecutive reaction cycles. Finally, GO/CS-pectinase was employed for guava juice clarification which exhibited the turbidity reduction up to 81 % after 75 min of treatment.

Ultrasound Assisted Extraction and Characterization of Bioactives From Verbascum thapsus Roots to Evaluate Their Antioxidant and Medicinal Potential.

Worldwide, Verbascum thapsus is used for the treatment of various ailments owing to the presence of bioactives of therapeutic potential. Current study was planned to extract bioactives from V thapsus roots using methanol and water as solvents under stimulated effect of ultrasonic waves and characterize them to evaluate their potential benefits. Proximate analysis explored the presence of significant contents of protein, fats, fiber, organic and inorganic minerals. Fourier transform infrared spectra and high-performance liquid chromatography chromatogram indicated the presence of different phytochemicals having antioxidant potential as evidenced by total phenolic contents, total flavonoids content and 2,2-diphenyl-1-picrylhydrazyl activity of both extracts. Both extracts displayed excellent antimicrobial potential against Staphylococcus aureus (S aureus) and Fusarium Solani (F solani). Aqueous and methanolic extracts exhibited higher inhibition of biofilm made by Bacillus subtilis (B subtilis) as 55.09 and 61.58%, respectively in comparison to biofilm of Escherichia coli (E coli) as 48.11 and 36.51%, respectively. Methanol extract exhibited anti-amylase activity (IC50 5.26 ± .31 µg/mL) with an inhibition rate of 68.11% whereas IC50 of aqueous extract was 6.59 ± .53 µg/mL with an inhibition rate of 63.53%. Inhibitory potential against α-glucosidase (IC50 3.70 ± .94 ppm) was demonstrated by methanol extract in comparison to aqueous extract (IC50 7.58 ± .15). The study concluded that V thapsus roots have significant medicinal potential due to the presence of variety of bioactive molecules and can be used in pharmaceutical preparations.

Nanoparticles encapsulation of Phoenix dactylifera (date palm) mucilage for colonic drug delivery.

Compressed tablet formation from granular drug require binder with Cohesiveness property. Plants mucilage as pharmaceutical excipients are available. In this study, biocompatible date palm mucilage was encapsulated with silver nano particles for sustained drug release to provoke an immune response. Nano formulated mucilage was characterized by UV/VIS, FTIR, XRD, SEM/EDX spectrophotometry. UV/VIS spectra revealed an intense surface plasmon resonance peak at 406 nm for spherical mono dispersed silver nano formulated mucilage resulted from efficient reduction of silver ions to AgNPs. Zeta sizer disclosed the emergence of single peak at 139.7 nm with 100% intensity. Crude mucilage exhibited number of peaks in the region of 4000-500 cm-1 by FT-IR spectroscopy whereas purified as well as nano formulated samples showed somewhat different pattern of peaks in addition to peaks of crude sample. XRD spectra of crude mucilage revealed somewhat regular pattern while purified and modified mucilage displayed irregular structure. In SEM analysis, crude mucilage was appeared as granular that turned into porous network with entangled tiny silver nano spheres. A controlled release of drug levofloxacin hemihydrate was evaluated using crude/ nano formulated mucilage as excipient. Nano formulated mucilage delayed the onset exposure of drug in gastric medium giving recommendations as value added bio binder for drug to the target organ.

Next-Generation Breeding Strategies for Climate-Ready Crops.

Climate change is a threat to global food security due to the reduction of crop productivity around the globe. Food security is a matter of concern for stakeholders and policymakers as the global population is predicted to bypass 10 billion in the coming years. Crop improvement via modern breeding techniques along with efficient agronomic practices innovations in microbiome applications, and exploiting the natural variations in underutilized crops is an excellent way forward to fulfill future food requirements. In this review, we describe the next-generation breeding tools that can be used to increase crop production by developing climate-resilient superior genotypes to cope with the future challenges of global food security. Recent innovations in genomic-assisted breeding (GAB) strategies allow the construction of highly annotated crop pan-genomes to give a snapshot of the full landscape of genetic diversity (GD) and recapture the lost gene repertoire of a species. Pan-genomes provide new platforms to exploit these unique genes or genetic variation for optimizing breeding programs. The advent of next-generation clustered regularly interspaced short palindromic repeat/CRISPR-associated (CRISPR/Cas) systems, such as prime editing, base editing, and de nova domestication, has institutionalized the idea that genome editing is revamped for crop improvement. Also, the availability of versatile Cas orthologs, including Cas9, Cas12, Cas13, and Cas14, improved the editing efficiency. Now, the CRISPR/Cas systems have numerous applications in crop research and successfully edit the major crop to develop resistance against abiotic and biotic stress. By adopting high-throughput phenotyping approaches and big data analytics tools like artificial intelligence (AI) and machine learning (ML), agriculture is heading toward automation or digitalization. The integration of speed breeding with genomic and phenomic tools can allow rapid gene identifications and ultimately accelerate crop improvement programs. In addition, the integration of next-generation multidisciplinary breeding platforms can open exciting avenues to develop climate-ready crops toward global food security.

Association of BDNF and SERT gene polymorphisms with depression among Pakistani population.

Brain-derived neurotrophic factor (BDNF) and serotonin transporter (SERT) is implicated in the adverse life events which lead to depression. The variation in genetic make-up of BDNF (Val66Met) and SERT (5'-HTTLPR) are potential biomarkers in the development of neuropsychiatric disorders including depression. The purpose of this study was to investigate the correlation of functional polymorphisms of BDNF and SERT genes with depression among Pakistani population. A total of 373 participants (204 cases with depressive episodes and 169 healthy controls) with age between 14 and 65yrs were recruited from Pakistani population. BDNF and SERT gene polymorphisms were genotyped using PCR-RFLP analysis. The result showed that lack of association of Val66Met (χ2: 3.596, p>0.05) and 5'-HTTLPR (χ2: 0.634, p>0.05) gene polymorphisms were found with depression. However, SERT 'SL' (OR: 1.150, 95%CI: 0.601-2.201) and BDNF 'AA' (OR: 1.651, 95%CI: 0.585-4.660) and 'GA' (OR: 2.279, 95%CI: 0.825-6.298) genotypes might be a risk genotypes for depression. Hence, it is concluded that the functional BDNF (Val66Met) and SERT (5'-HTTLPR) gene polymorphisms may not be associated with depression. Replication studies on these polymorphisms with large sample size are needed.

Evaluation of wound healing effects of Syzygium cumini and laser treatment in diabetic rats.

This study was aimed to investigate the antioxidant effects of Syzygium cumini (S. cumini) seeds extract along with wound healing score in correlation to glutathione and blood glucose levels in diabetic rats. Sprague-Dawley rats were divided into 8 groups (n=6) and diabetes was induced by a single intraperitoneal injection of streptozotocin (40 mg kg-1 body weight). An alcoholic extract of S. cumini was administered to punch plier induced wounded rats and changes in serum glutathione levels, wound healing score and blood glucose levels were examined. Laser treatment of 500 mW for 5 minutes was given once a day for 12 days at 810 and 630 nm respectively. Statistical analysis was performed using one way ANOVA. A p-value <0.05 was considered significant and p-value <0.001 was considered highly significant. There was significant increase in glutathione levels and wound healing score when S. cumini extract was administered oral and topical along with topical laser therapy. There was significant reduction in the blood glucose levels upon administration of S. cumini extract in diabetic rats. This study concludes that there was a positive relation between the glutathione levels and wound healing score, since there was increase in wound healing score with the increase in the glutathione levels.

Synthesis, characterization, antibacterial, hemolytic and thrombolytic activity evaluation of 5-(3-chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives.

A novel series of 5-(3-Chlorophenyl)-2-((N-(substituted)-2-acetamoyl)sulfanyl)-1,3,4-oxadiazole derivatives was efficiently synthesized and screened for antibacterial, hemolytic and thrombolytic activities. The molecule 7c remained the best inhibitor of all selected bacterial strains and furthermore possessed very low toxicity, 8.52±0.31. Compound 7a 7b and 7f showed very good thrombolytic activity relative to Streptokinase employed as reference drug. In addition to low toxicity and moderately good thrombolytic activity, the synthesized compounds possessed excellent to moderate antibacterial activity, relative to ciprofloxacin. All compounds especially 7b and 7f can be consider for further clinical studies and might be helpful in synthesis of new drugs for treatment of cardiovascular diseases.

Autism Cognizance: A dilemma among medical and Allied Medical practitioners.

OBJECTIVES: To determine the awareness about autism among Medical and Allied-Medical Practitioners. METHODS: This cross-sectional survey recruited a sample of n=300 participants including n=150 Medical and n=150 Allied-Medical practitioners using convenience sampling from Benazir Bhutto Hospital and Autism Resource Centre, Rawalpindi, Pakistan between 20th May 2018 to 20th October 2018. Sample included both genders, aged 21 to 50 years. Basic demographic sheet and Knowledge about Childhood Autism among Health Workers (KCAHW) Questionnaire was used to collect data. Statistical analysis was done using SPSS 21. RESULTS: Study revealed the total mean KCAHW score of 15.20 ± 5.17 and 8.84 ± 6.31 for Allied-Medical and Medical practitioners respectively. While the Domain-I mean KCAHW scores was 6.28±2.10 and 3.68±2.41; Domain-II score 0.86 ± 0.35 and 0.45 ± 0.50; Domain-III score 3.28 ± 1.00 and 1.91 ± 1.65; and Domain-IV score of 4.83 ±1.72 and 2.80 ± 1.75 for Allied-Medical and Medical practitioners respectively. CONCLUSION: The present study shows that there is significant awareness regarding autism among Allied-Medical compared to Medical practitioners.

Progress and prospects in the management of bacterial infections and developments in Phytotherapeutic modalities.

The advent of antibiotics revolutionized medical care resulting in significantly reduced mortality and morbidity caused by infectious diseases. However, excessive use of antibiotics has led to the development of antibiotic resistance and indeed, the incidence of multidrug-resistant pathogens is considered as a major disadvantage in medication strategy, which has led the scholar's attention towards innovative antibiotic sources in recent years. Medicinal plants contain a variety of secondary metabolites with a wide range of therapeutic potential against the resistant microbes. Therefore, the aim of this review is to explore the antibacterial potential of traditional herbal medicine against bacterial infections. More than 200 published research articles reporting the therapeutic potential of medicinal plants against drug-resistant microbial infections were searched using different databases such as Google Scholar, Science Direct, PubMed and the Directory of Open Access Journals (DOAJ), etc., with various keywords like medicinal plants having antibacterial activities, antimicrobial potentials, phytotherapy of bacterial infection, etc. Articles were selected related to the efficacious herbs easily available to local populations addressing common pathogens. Various plants such as Artocarpus communis, Rheum emodi, Gentiana lutea L., Cassia fistula L., Rosemarinus officinalis, Argemone maxicana L, Hydrastis canadensis, Citrus aurantifolia, Cymbopogon citrates, Carica papaya, Euphorbia hirta, etc, were found to have significant antibacterial activities. Although herbal preparations have promising potential in the treatment of multidrug-resistant bacterial infection, still more research is required to isolate phytoconstituents, their mechanism of action as well as to find their impacts on the human body.

An alternative approach to treat obesity with leptogenic polyherbal formulation obesecure: A randomized clinical trial study.

Obesity is a common disease of developing countries, including Pakistan. Obesity is a risk factor for many diseases which can be life threatening or making the person unable to perform daily routine work. In the current study, clinical trials were designed to evaluate the effects of medical intervention by comparing the effects of placebo control drug "Plasicure" with the herbal medicinal formulation "Obesecure". The test drug formulation was designed on the basis of the screening study for Leptogenic drugs. To evaluate the safety of the test drug, the toxicity index and the safety profile of test formulation was assessed on animal models. The drug was found safe for further clinical study. Randomized Controlled Clinical Trials were conducted. The statistical analysis was carried out by the application of Two-Way Repeated Analysis of Variance test. The clinical findings of randomized controlled trial revealed that the test drug was Leptogenic and effective in weight reduction as compared to control drug Plasicure therapy as the p-value deduced was 0.001 in leptin level and 0.000 in case of BMI after the conduction of Two-Way Repeated Analysis of Variance test. Hence it is concluded that obscure therapy is more significant than control drug Plasicure therapy in the management and treatment of obesity.

Hypophagic and weight reducing effect of Momardica charinta fruit by Enhancing 5-HT neurotransmitter in rats brain.

Momardica charint seed as vegetable and folk medicine in Pakistan, India, China, Bangladesh and other Asian countries Momardica charinta also known as Kerala, bittergourd ,balsam pear. It possesses many biological active constituents including glycosides, saponins, phenolic and flavonoids compound, protein, triterpenes, steroid, saponins, alkaloid. It also contain thiamine ,beta carotene, folate, riboflavin, calcium, iron, potassium, zinc and fiber. Several studies have been done to show medicinal importance of its fruit which has different biological functions such as anti-diabetes antihypertension, antiviral, antibacterial and antifungal infection, anti-tumorous as well as anti-carcinogenic effects. The present research is big contribution of Momardicacharinta activity as weight reducing plant through serotonergic neurotransmitter Decrease in body weight and food intake might be due to increased concentration of serotonin in their respective receptors in brain, which produce hypophagic effect in rats treated with water extract of Momardicacharinttia. More animal and human trials needed to confirm, the safety and antiobesity effect of MC and the role of neurotransmitter involve in reduction of body weight.

Awareness and current knowledge of epilepsy.

Epilepsy is a severe neural disorder that affects approximately fifty million individuals globally. Despite the fact that for most of the people with epilepsy, convulsions are better controlled by current accessible antiepileptic medicines, yet there are more than 30% of individuals affected with medically intractable epilepsy and around 30-40% of all patients with epilepsy affected by many adverse reactions and convulsion resistance to the present antiepileptic drugs. Consequently, various scientists attempt to develop new strategies to treat epilepsy, for instance, to find out novel antiepileptic ingredients from traditional medicines. This work aims to present a complete summary of natural medicines prescribed as antiepileptic agents all over the world by ethnic groups and different tribes. We undertook an extensive bibliographic analysis by searching peer reviewed papers and classical textbooks and further consulting well accepted worldwide scientific databases. We carried out PubMed, EMbase and CENTRAL searches by means of terms such as "antiepileptic" and "anti-convulsant" activity of plants. Medicinal plants have been prescribed to treat epilepsy and have been recognized as antiepileptic medicines. In this review, a variety of herbs have been reviewed for thorough studies such as Cuminum cyminum, Butea monosperma, Solanum americanum, Anacyclus pyrethrum, Leonotis leonurus, Elaeocarpus ganitrus and Angelica archangelica. This paper shows that it was high time experimental studies are increased to obtain novel potential active principles from medicinal plants. Plant extracts and their chemical constituents should be further evaluated to clarify their mechanisms of action. This paper provides a solid base upon which to further investigate the clinical efficacy of medicinal plants that are both currently prescribed by physicians as traditional antiepileptic agents, but also could be effective as an antiepileptic drug with further research and study.

Therapeutic potential of medicinal plants for the management of scabies.

Sarcoptes scabiei (S. scabiei), a parasite mite which causes scabies disease resulting in serious public health concern. The long-term scabies disease can lead to complications such as septicemia, acute post-streptococcal glomerulonephritis, heart disease, and secondary infections. Timely treatment to the affected patients is required to control the disease and get rid of the causative agent. Delayed diagnosis and inappropriate treatment can lead to serious consequences. The most common treatment strategy is the use of allopathic medicines which can immediately relieve the patient but have the drawback of side effects. The safe and cost-effective alternative treatment strategy is the use of medicinal plants which have beneficial therapeutic potential against variety of diseases due to the presence of many bioactive phytoconstituents with no or minimal side effects. For the present review, the published articles describing scabies disease and its phytotherapeutic modalities were searched through different data bases including Google Scholar, PubMed, Medline, and ScienceDirect using the keywords like S. scabiei, prevalence of scabies disease, and phytotherapy of scabies. A large number of medicinal plants, such as Melaleuca alternifolia, Curcuma longa, Azadirachta indica, Rosmarinus officinalis, Capsicum annuum, Cinnamomum camphor, Solanum nigrum, and Eupatorium perfoliatum, have been reviewed for the promising future treatments of scabies. All the studied plants have many bioactive compounds with potential therapeutic effects against scabies and can be utilized for therapeutic purposes for this disease. This literature study has limitations because of the lack of sufficient data due to limited pre-clinical trials in this particular area. This review provides a baseline to explore the therapeutic potential of these medicinal plants against skin diseases. However, extensive studies are required to identify, authenticate, and characterize the bioactive compounds present in these plants which may lead to value addition in pharmaceutical industries providing the cost-effective way of treatment with minimal side effects.

Chemical constituents, experimental and clinical pharmacology of Rosa damascena: a literature review.

CONTEXT: Rosa damascena Mill. is prescribed for the management of chest and abdominal pain, constipation, digestive disorders, menstrual bleeding and liver ailments. OBJECTIVE: The current review compiles up to date and complete information of whole plant of R. damascena with particular emphasis on its numerous scientifically proved pharmacological effects, traditional and folk medicinal uses. KEY FINDING: The data on the pharmacological effects of R. damascena were collected from various databases such as PubMed, Wiley Online Library, Elsevier and Web of Science using the keywords like phytoconstituents, pharmacology, medicinal uses and biological activity of R. damascene. Rosa damascena has a wide spectrum of bio-pharmacological activity like antidepressant, hypoglycaemic, anti-inflammatory, analgesic, antioxidant and antimicrobial. The main ingredients of R. damascena essential oil responsible for pharmacological activity are geraniol and citronellol. Its uses have been widely accepted in traditional system of medicines for the management of numerous diseases of human beings in different dosage forms. SUMMARY: Rosa damascena has a significant place in traditional system of medicine. It is cost-effective and an important plant with curative application in contemporary medicine. Further studies on the characterization of chemical constituents and scientific basis of pharmacological activity of R. damascena should be carried out to evaluate its impact on traditional system of medicines. Large-scale preclinical and clinical trials will be beneficial in investigating the mechanism of the therapeutic potential of R. damascene to explore its uses in pharmaceutical industries.

Role of medicinal plants in HIV/AIDS therapy.

Human immunodeficiency virus (HIV) causes the potentially life-threatening and chronic disease called acquired immune deficiency syndrome (AIDS). The main target of this viral disease is to suppress the immune system and make the body unresponsive to external stimuli. According to global health observatory data since epidemic, more than 78 million people were affected by HIV and 39 million people died globally. Until 2017, 36.5 million people were living with HIV. An estimated 0.8% (0.6%-0.9%) of adults aged 15-49 years worldwide is living with HIV. The World Health Organization (WHO) reported that the African region remains most severely affected, with nearly one in every 25 adults (4.1%) living with HIV and accounting for nearly two-thirds of the people living with HIV worldwide. WHO reported that globally only 21.7 million (19.1 million-22.6 million) people have had access to antiretroviral therapy up to 2017. Currently, antiretroviral therapy (ART) is available for the control of HIV but has serious associated side effects such as lipodystrophy. Because of the limitations, associated with ART, researchers throughout the world are trying to explore and develop more reliable and safe drugs from natural resources to manage HIV infection. A wide range of medicinal plants have been studied and have reported significant potential against HIV. Plants like Rheum palmatum L., Rheum officinale, Trigonostem axyphophylloides, Vatica astrotricha, Vernonia amygdalina, Hypoxias pelargonium, Sidoides hemerocallidea and Sutherlandia frutescens etc. have high efficacy to cure HIV. The exact mechanism of action is still not known but various phytoconstituents isolated from medicinal plants such as alkaloids, flavonoids, polyphenols, terpenoids, tannins, proteins and coumarins have the potential to interrupt the life cycle of HIV as well as act as immunomodulators to enhance the immune system of infected patients with no well reported side effects. It could be concluded that medicinal plants have potential for the management of HIV/AIDS but more studies are needed to reveal rigorous efficacy and safety concerns by conducting clinical trials at vast level to explore therapeutic impact of medicinal plants.

Determination of Arylamine N-Acetyltransferase 2 Acetylation Genotype by PCR and Phenotyping Using Dapsone Through High-Pressure Liquid Chromatography Assay: A Gender Wise Study.

The main aim of the study was to establish the acetylation status of local population of Pakistan by N-acetyltransferase 2 (NAT2) enzyme and to find out the concordance between phenotypic and genotypic methods for the determination of NAT2 acetylation. Gender-wise comparison of selected healthy male and female volunteers aged greater than 18 years was also conducted to see the effect of sex on NAT2 acetylation. Phenotypically, the rate of acetylation was determined by high-pressure liquid chromatography with dapsone (DDS) probe drug, while genotypically, NAT2 acetylation was determined by using specific primers for NAT2 variant alleles (M1, M2, and M3) amplified in separate polymerase chain reactions. High-pressure liquid chromatography results indicated 64% of the male volunteers to be fast acetylators while 36% were slow acetylators, while ratio of fast and slow acetylators for female was found to be 66% and 34%, respectively. Genotypically, the ratio of fast and slow for male was 60% and 40% and for female was 66% and 34%, respectively. The distribution of 3 NAT2 variant alleles was found in invariable number. For male volunteers, the highest frequency distribution showed by M2 allele was 56%, while for M1 and M3 the frequency was 32% and 12%, respectively, and for female volunteers highest frequency (51%) was shown by the M2 variant allele while lowest frequency (18%) was shown by M3 allele. There was the 94% concordance between the DDS phenotype and genotype. Gender effect on the acetylation was found to be nonsignificant (P > .05). Therefore, it is concluded that NAT2 acetylation rate can be used to check in vivo acetylation status with dapsone as probe drug. It is concluded that NAT2 acetylation rate was unaffected by gender and can be used to check in vivo acetylation status with dapsone as probe drug, which is inexpensive and less time-consuming.

Correlation of metformin with intravenous iodinated contrast media and precautions.

To discuss metformin and iv-contrast induced acute renal failure with its reported cases worldwide, associated risk factors and precautions that can be taken to reduce this tragedy & to address this sensitive issue to my technologist family working in clinical situations. As these studies were observational studies and just report contrast induced nephrotoxicity in different countries by analyzing patients data. By Personal experience or by analyzing data available on PACS (Picture archiving and communication system) most commonly available in Hospitals now a days, that is why these studies did not use any scientific procedure. In our study, we collected opinions of Senior Doctors about use of Metformin before and after contrast study. All Doctors were agreed upon investigation of serum creatinine before contrast study. Doctors were not agreed on single opinion but surely they agreed on stop of Metformin before and after procedure. They said its responsibility of imaging technologist or Radiologist to guide patient about this problem. Diabetic patients using Metformin are at high risk of acute renal acidosis if they are undergoing for iodinated contrast study.