Deciphering the emerging role of phytocompounds: Implications in the management of drug-resistant tuberculosis and ATDs-induced hepatic damage.

Tuberculosis is a disease of poverty, discrimination, and socioeconomic burden. Epidemiological studies suggest that the mortality and incidence of tuberculosis are unacceptably higher worldwide. Genomic mutations in embCAB, embR, katG, inhA, ahpC, rpoB, pncA, rrs, rpsL, gyrA, gyrB, and ethR contribute to drug resistance reducing the susceptibility of Mycobacterium tuberculosis to many antibiotics. Additionally, treating tuberculosis with antibiotics also poses a serious risk of hepatotoxicity in the patient's body. Emerging data on drug-induced liver injury showed that anti-tuberculosis drugs remarkably altered levels of hepatotoxicity biomarkers. The review is an attempt to explore the anti-mycobacterial potential of selected, commonly available, and well-known phytocompounds and extracts of medicinal plants against strains of Mycobacterium tuberculosis. Many studies have demonstrated that phytocompounds such as flavonoids, alkaloids, terpenoids, and phenolic compounds have antibacterial action against Mycobacterium species, inhibiting the bacteria's growth and replication, and sometimes, causing cell death. Phytocompounds act by disrupting bacterial cell walls and membranes, reducing enzyme activity, and interfering with essential metabolic processes. The combination of these processes reduces the overall survivability of the bacteria. Moreover, several phytochemicals have synergistic effects with antibiotics routinely used to treat TB, improving their efficacy and decreasing the risk of resistance development. Interestingly, phytocompounds have been presented to reduce isoniazid- and ethambutol-induced hepatotoxicity by reversing serum levels of AST, ALP, ALT, bilirubin, MDA, urea, creatinine, and albumin to their normal range, leading to attenuation of inflammation and hepatic necrosis. As a result, phytochemicals represent a promising field of research for the development of new TB medicines.

Follicular Thyroid Carcinoma in a Developing Country: A 10-Year Retrospective Study.

Background The most common endocrine tumor is thyroid cancer. Follicular thyroid carcinoma (FTC) accounts for 5-10% of all thyroid cancers. Patients with FTC frequently present with more advanced diseases and a higher occurrence of distant metastases because of the propensity of vascular invasion. FTC is mainly treated with surgery while radioactive iodine (RAI) therapy is the main adjuvant therapy according to the American Thyroid Association guidelines. Methodology This was a retrospective observational study of FTC patients aged 18 and above conducted at a tertiary care hospital in Karachi from January 01, 2010 to December 31, 2019. Results A total of 404 patients with thyroid carcinoma were sorted, of which 40 (10.1%) were FTC cases. Overall, 50% of the patients were in the age group of 41-60 years, and the female-to-male ratio was 1.5:1. The majority of patients (60%) presented with neck swelling, followed by bone and lung metastasis in 20% and compressive symptoms in another 20%. On fine needle aspiration cytology (FNAC), 50% had Bethesda category III-IV nodules while 10% had Bethesda category II. Overall, 50% had a total thyroidectomy while 50% had a lobectomy followed by a completion thyroidectomy. On histopathology, 23 (57.5%) patients had minimally invasive FTC while 17 (42.5%) had widely invasive FTC. A total of 17 (42.5%) patients had received RAI 30-100 mCi while 10 (25%) received more than 100 mCi. Conclusions FTC can present with both local or metastatic symptoms. The atypical presentation of metastatic FTC should be considered, diagnosed, and managed early to limit mortality and morbidity. Ultrasound is the best diagnostic investigation of choice followed by FNAC. Surgery is the mainstay of treatment and should be followed by RAI in select cases. Thus, understanding the trend of FTC and proper planning and utilization of the resources will help developing countries in effectively treating the FTC.

Primary Hyperparathyroidism: Experience from a Tertiary Care Centre in Pakistan.

OBJECTIVE: To study the clinical, biochemical and radiological features and management outcomes of patients with primary hyperparathyroidism. METHODS: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, Pakistan and comprised data of patients with primary hyperparathyroidism from 2008 to 2017. RESULTS: Out of 103 patients, 83(80.6%) were female. Overall mean age was 59.3±16.2 years. Musculoskeletal manifestations were seen in 60(58.3%) patients and renal manifestations in 28(27.2%). Ostieits fibrosa cystica was found in 04(3.88%) patients. Overall, Ultrasound neck and sestamibi scan localized the lesion in 66 (64.1%) and 77 (76.2%) patients respectively. Among 79 patients who underwent surgery, 67 (84.8%) patients had an adenoma, 05 (6.3%) had hyperplasia and 02(2.53%) patients had parathyroid carcinoma whereas histopathology was inconclusive in 5 (6.32%) out of the 79 surgically treated patients. Disease recurrence was seen in 13 out of 79(16.45%) patients who underwent surgery. CONCLUSION: Primary hyperparathyroidism is associated with significant morbidity in our population. Targeted measures like improving patient awareness, routine calcium screening, vitamin D supplementation and a high index of suspicion by the clinician may help in early diagnosis of the condition and thus reduce morbidity.

Association of vitamin D deficiency with poor glycaemic control in diabetic patients.

OBJECTIVE: An association between serum levels of vitamin D and glycaemic control in type-2 diabetes mellitus (DM) patients has been reported in some of the studies carried out in the West. However, there are no reports on this relationship in Pakistani diabetic patients. The aim of this study was to ascertain whether vitamin D levels have any influence on glycaemic control in Pakistani patients with type-2 DM. METHODS: In a cross-sectional survey, relationship between serum levels of 25-hydroxy vitamin D (25(OH)D) and glycated haemoglobin (HbA1C) was examined in 141 type-2 diabetic patients including 102 males and 39 females; age range 22 to 70 years, visiting the Aga Khan University Hospital during July 2013-April 2014. Venous blood was collected and analyzed for serum/plasma levels of 25(OH)D and related biomarkers using kit methods. HbA1C levels <7.0% and >7.0% were taken as indicators of good and poor glycaemic control, respectively. An association between 25(OH)D and HbA1C was investigated using regression analysis. RESULTS: Percent vitamin D deficiency (serum level of 25(OH)D < 20 ng/ml) was significantly higher in patients with poor glycaemic control compared to patients with good glycaemic control (58.7% vs. 30.6%; p-value=0.006). Binary logistic regression analysis revealed positive association between vitamin D deficiency and poor glycaemic control while adjusting for BMI, serum levels of albumin, alanine aminotransferase and alkaline phosphatase (OR, 4.86 (95% CI, 1.9-11.9; p-value<0.001). CONCLUSIONS: The association between vitamin D deficiency and abnormal HbA1C in Pakistani diabetic patients is suggestive that patients with hypovitaminosis D could benefit from vitamin D supplementation.

Baseline stimulated thyroglobulin level as a good predictor of successful ablation after adjuvant radioiodine treatment for differentiated thyroid cancers.

BACKGROUND: To determine the predictive value of the baseline stimulated thyroglobulin (STg) level for ablation outcome in patients undergoing adjuvant remnant radioiodine ablation (RRA) for differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: This retrospective study accrued 64 patients (23 male and 41 female; mean age of 40±14 years) who had total thyroidectomy followed by RRA for DTC from January 2012 till April 2014. Patients with positive anti-Tg antibodies and distant metastasis on post-ablative whole body iodine scans (TWBIS) were excluded. Baseline STg was used to predict successful ablation (follow-up STg<2 ng/ml, negative diagnostic WBIS and negative ultrasound neck) at 7-12 months follow-up. RESULTS: Overall, successful ablation was noted in 37 (58%) patients while ablation failed in 27 (42%). Using the ROC curve, a cut-off level of baseline STg level of ≤14.5 ng/ml was found to be most sensitive and specific for predicting successful ablation. Successful ablation was thus noted in 25/28 (89%) of patients with baseline STg≤14.5 ng/ml and 12/36 (33%) patients with baseline STg>14.5 ng/ml ((p value<0.05). Age>40 years, female gender, PTS>2 cm, papillary histopathology, positive cervical nodes and positive TWBIS were significant predictors of ablation failure. CONCLUSIONS: We conclude that in patients with total thyroidectomy followed by I-131 ablation for DTC, the baseline STg level is a good predictor of successful ablation based on a stringent triple negative criteria (i.e. follow-up STg <2 ng/ ml, a negative DWBIS and a negative US neck).

South Asian women with diabetes: Psychosocial challenges and management: Consensus statement.

Diabetes is the ninth leading cause of death in women globally. In South Asians mortality in women with diabetes stands second highest. There is a marked gender discrimination which is faced by women across South Asia esp in access to services and support for diabetes, resulting in high rates of morbidity and mortality in women with diabetes. The most important risk factor identified for the diabetes epidemic is obesity along with genetic susceptibility. Lack of health care, social and cultural disparity, discrimination at work, disparity in marriage, restricted medical facilities are prevalent. Diabetes and depression are common in women. Increasing age, low level of education, low socioeconomic conditions, difficulties posed in finding partners, frequent divorce and family history of psychiatric illness are significant risk factors for diabetes and depression. Such patients usually have poor metabolic control, higher complication rates, increased healthcare costs, lost productivity, lower quality of life as well as increased risk of death. Preconception counseling should be incorporated in the routine diabetes clinic visit for all women of childbearing potential. Women with diabetes should have information and access to contraception. Proper family planning counseling and psychological support can help stop practices such as female foeticide and multiple pregnancies. Psychological support to patients and their families are needed to break the barrier. There is emerging evidence that women with diabetes are more prone to untoward outcomes as compared to men. Central obesity, metabolic syndrome and the polycystic ovary syndrome show ethnic specific differences in South Asian women. Optimal sexuality is an integral part of holistic health. Shortage of trained female health care professionals, lack of privacy in over-crowded health care facilities, a social taboo attached to such matters, and lack of confidence in patients contribute to the neglect of sexual issues in women attending diabetes clinics across South Asia. Guidelines for counselling in female sexual dysfunction, written in culturally appropriate manner for South Asia, are needed. Diabetes affects women more severely because of their unique biological, cultural and socioeconomic circumstances. Women have limited access to health care facilities because of illiteracy, ignorance and negative social customs. Transcending the gender hierarchy and inequality is a formidable challenge. Sensitising men, empowering women on self care and providing peer support maybe the answer to this challenge. It is essential for health care providers to use appropriate coping mechanism such as building psychological contact with the patient, including family and friends as part of social support and empower patient with complete process of managing diabetes. Increasing awareness through the media, seminars, posters, group discussions and education, regular monitoring and consulting the doctor, support group for women and facilities for aerobic exercises are recommended. The health care systems should consider custom-designed prevention and control programs tailored for women based on local and regional attitudes on health care, cultural beliefs, and available social support systems. Policies that empower adolescent girls and young women to take control of their metabolic management must be encouraged. Provision of gender specific diabetes education with a holistic life-cycle approach is recommended.

A study on antioxidant and apoptotic effect of Azadirachta Indica (neem) in cases of cervical cancer.

PURPOSE: To study the anti-oxidant properties of neem (Azadirachta indica) in inducing apoptosis of cervical cancer cells and estimation of caspase activity and TNF-α and IFN-γ levels in monocytes of cervical cancer patients and controls. METHODS: Monocytes were cultured from blood samples of 65 study cases and 30 controls for the estimation of caspase 3, 8 and 9 with specific inhibitors and TNF-α and IFN-γ levels in culture supernatant of monocytes. Two cervical biopsies were taken from 18 cases of moderately differentiated SCC. One biopsy was formalin fixed for histopathology and the other for tissue culture was kept in RPMI-1640 medium to evaluate the apoptotic effect of neem extract on malignant cells. RESULTS: Neem-treated monocytes from cervical cancer patients showed high activity levels of caspase 3, 8, and 9. A decrease in TNF-α and an increase in IFN-γ levels was seen in culture supernatant of monocytes. Cyto- and histomorphology of neem-treated cervical cancer cells exhibited increased apoptosis. CONCLUSION: Neem is a potent inducer of apoptosis in biopsies of cervical cancer patients.

Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males.

OBJECTIVE: To investigate the impact of Withania somnifera roots on semen profile, oxidative biomarkers, and reproductive hormone levels of infertile men. DESIGN: Prospective study. SETTING: Departments of Biochemistry and Urology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India. PATIENT(S): Seventy-five normal healthy fertile men (control subjects) and 75 men undergoing infertility screening. INTERVENTION(S): High-performance liquid chromatography assay procedure for quantization of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma were estimated by standard spectrophotometric procedures. Estimation of T, LH, FSH, and PRL in blood serum by RIA methods. MAIN OUTCOME MEASURES(S): Before and after the treatment, seminal plasma biochemical parameters, antioxidant vitamins, and serum T, LH, FSH, and PRL levels were measured. RESULT(S): Withania somnifera inhibited lipid peroxidation and protein carbonyl content and improved sperm count and motility. Treatment of infertile men recovered the seminal plasma levels of antioxidant enzymes and vitamins A, C, and E and corrected fructose. Moreover, treatment also significantly increased serum T and LH and reduced the levels of FSH and PRL. CONCLUSION(S): The treatment with W. somnifera effectively reduced oxidative stress, as assessed by decreased levels of various oxidants and improved level of diverse antioxidants. Moreover, the levels of T, LH, FSH and PRL, good indicators of semen quality, were also reversed in infertile subjects after treatment with the herbal preparation.

Effect of Mucuna pruriens on semen profile and biochemical parameters in seminal plasma of infertile men.

OBJECTIVE: To investigate the impact of Mucuna pruriens seeds on semen profiles and biochemical levels in seminal plasma of infertile men. DESIGN: Prospective study. SETTING: Departments of Biochemistry and Obstetrics and Gynecology, King George's Medical University, Lucknow, India. PATIENT(S): Sixty normal healthy fertile men (controls) and 60 men undergoing infertility screening. INTERVENTION(S): High-performance liquid chromatography assay procedure for quantitation of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma, namely lipids, fructose, and vitamin C, were estimated by standard spectrophotometric procedures. MAIN OUTCOME MEASURE(S): Before and after the treatment, seminal plasma lipid profile, lipid peroxide, fructose, and antioxidant vitamin levels were measured. RESULT(S): Treatment with M. pruriens significantly inhibited lipid peroxidation, elevated spermatogenesis, and improved sperm motility. Treatment also recovered the levels of total lipids, triglycerides, cholesterol, phospholipids, and vitamin A, C, and E and corrected fructose in seminal plasma of infertile men. CONCLUSION(S): Treatment with M. pruriens increased sperm concentration and motility in all the infertile study groups. Oligozoospermic patients recovered sperm concentration significantly, but sperm motility was not restored to normal levels in asthenozoospermic men. Furthermore, in the seminal plasma of all the infertile groups, the levels of lipids, antioxidant vitamins, and corrected fructose were recovered after a decrease in lipid peroxides after treatment. The present study is likely to open new vistas on the possible role of M. pruriens seed powder as a restorative and invigorating agent for infertile men.