The role of p53 and ki67 in predicting clinical outcome in breast cancer patients.

Background: ">ki67 may be used as a proliferative index in addition to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) negative status. p53 gene expression is a well-known biomarker in breast cancer and its role in predicting clinical outcome remains unclear. The current study aimed to determine the relationship between p53 gene mutation and ki67 expression, their clinical characteristics, and overall survival (OS), and to differentiate the significance of p53 and ki67 as the prognostic value in breast cancer patients. Methods: ">In this study, 135 patients were enrolled in the study from December 2015 to May 2017. Medical records for all patients were reviewed prospectively. The inclusion criteria included age more than 18 years with histologically proven breast cancer and willingness to be enrolled in p53 genetic study. Exclusion criteria included dual malignancy, male breast cancer, with a loss to follow-up during the study. Results: ">The mean survival of patients with ki67 ≤20 index was 42.7 months (95% confidence interval [CI] 38.7-46.7) and 129 months (95% CI 101.3-157.2) in patients with ki67 >20. The mean OS was 145 months (95% CI 105.6-185.5) in the p53 wild-type group and 106 months (95% CI 78.0-133.0) in the p53 mutated group, as illustrated. Conclusion: ">Our results indicated that p53 mutational status and high ki67 might have an essential impact on overall survival, with p53 mutated patients having a poorer outcome than p53 wild type patients.

Bioplatforms in liquid biopsy: advances in the techniques for isolation, characterization and clinical applications.

Tissue biopsy analysis has conventionally been the gold standard for cancer prognosis, diagnosis and prediction of responses/resistances to treatments. The existing biopsy procedures used in clinical practice are, however, invasive, painful and often associated with pitfalls like poor recovery of tumor cells and infeasibility for repetition in single patients. To circumvent these limitations, alternative non-invasive, rapid and economical, yet sturdy, consistent and dependable, biopsy techniques are required. Liquid biopsy is an emerging technology that fulfills these criteria and potentially much more in terms of subject-specific real-time monitoring of cancer progression, determination of tumor heterogeneity and treatment responses, and specific identification of the type and stages of cancers. The present review first briefly revisits the state-of-the-art technique of liquid biopsy and then proceeds to address in detail, the advances in the potential clinical applications of four major biological agencies present in liquid biopsy samples (circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), exosomes and tumor-educated platelets (TEPs)). Finally, the authors conclude with the limitations that need to be addressed in order for liquid biopsy to effectively replace the conventional invasive biopsy methods in the clinical settings.

Evaluation of safety and efficacy profile of Nigella sativa oil as an add-on therapy, in addition to alpha-keto analogue of essential amino acids in patients with chronic kidney disease.

Chronic kidney disease (CKD) encompasses a spectrum of different pathophysio- logic processes associated with abnormal kidney function. When it reaches end-stage renal disease (ESRD), the only option is dialysis and renal transplantation. This is unaffordable by most patients. Hence, newer treatment modalities are being looked for, which can slow down the progression of CKD and delay the development of ESRD. This study aimed to evaluate the efficacy and safety of Nigella sativa oil as an add-on therapy in addition to alpha-keto analogue of essential amino acids in patients with CKD Stages 3 and 4. The study was conducted at a tertiary care center in North India on patients with CKD Stages 3 and 4. It was a prospective, comparative, and open-labeled study. One hundred and fifty patients were enrolled and were randomly divided into two interventional groups. Fourteen patients were lost to follow-up. Group I (control) which had 66 patients received conservative management of CKD consisting of alpha-keto analogue (600 mg tablet three times a day), whereas Group II (test) which had 70 patients received conservative management along with alpha-keto analogue and N. sativa oil (2.5 mL, per orally, once daily) for 12 weeks. Hemogram, renal function, and serum electrolyte tests were done, and adverse events were recorded at baseline and at4, 8, and 12 weeks of treatment. After 12 weeks of treatment, there was a marked improvement in clinical features and biochemical parameters in both the control and test groups. There were a significant reduction in blood urea, serum creatinine, and 24-h total urine protein and a significant improvement in 24-h total urine volume and glomerular filtration rate. N. sativa oil supplementation along with alpha-keto analogue is more more efficacious and safe in delaying the progression of disease patients with CKD Stages 3 and 4.

Emerging biomarkers and clinical significance of HPV genotyping in prevention and management of cervical cancer.

Cervical cancer is a growing and serious problem world-wide in women, but more acute in developing countries especially in Indian subcontinent. The main causative agent for the disease is Human Papilloma Virus (HPV). The history of the cervical cancer goes back to eighteenth century as the HPV infection is reported since 1800s. Presently, the genetic structure of HPV is well defined. Several screening tests including cytology and visual based screening and high risk HPV testing are available. Also available are various clinical and commercial diagnostic tests. However due to the lack of awareness and population-based screening programs, the morbidity and mortality rate is alarmingly high. There are new emerging biomarkers including E6/E7 mRNA, p16ink4a, markers of aberrant S-phase induction, chromosomal abnormalities and miRNAs along with advanced genotyping methods. These markers have clinical significance and are helpful in disease prevention and management. Further, recent advancement in the field of metagenomics has increased the prospects of identifying newer microbes, viruses hitherto reported thus far in the context of HPV infection. Analysis of HPV cases using modern tools including genotyping using more powerful biomarkers is envisaged to enhance the prospects of early diagnosis, better prognosis, more reliable treatment and eventual management of the disease.

Nanotechnology-Based Approach in Tuberculosis Treatment.

Tuberculosis, commonly known as TB, is the second most fatal infectious disease after AIDS, caused by bacterium called Mycobacterium tuberculosis. Prolonged treatment, high pill burden, low compliance, and stiff administration schedules are factors that are responsible for emergence of MDR and XDR cases of tuberculosis. Till date, only BCG vaccine is available which is ineffective against adult pulmonary TB, which is the most common form of disease. Various unique antibodies have been developed to overcome drug resistance, reduce the treatment regimen, and elevate the compliance to treatment. Therefore, we need an effective and robust system to subdue technological drawbacks and improve the effectiveness of therapeutic drugs which still remains a major challenge for pharmaceutical technology. Nanoparticle-based ideology has shown convincing treatment and promising outcomes for chronic infectious diseases. Different types of nanocarriers have been evaluated as promising drug delivery systems for various administration routes. Controlled and sustained release of drugs is one of the advantages of nanoparticle-based antituberculosis drugs over free drug. It also reduces the dosage frequency and resolves the difficulty of low poor compliance. This paper reviews various nanotechnology-based therapies which can be used for the treatment of TB.

Protective role of Nigella sativa in diabetic nephropathy: A randomized clinical trial.

This study aims to evaluate efficacy and safety of Nigella sativa oil supplementation in patients with chronic kidney disease Stage 3 and 4 due to diabetic nephropathy. It was a prospective, comparative, and open-label study. Patients were randomized into two groups. Group 1 (Control) received conservative management of diabetic nephropathy, whereas Group 2 (Test) received N. sativa oil (2.5 mL, once daily and per orally) along with conservative management for 12 weeks. Blood glucose, hemogram, and kidney function test were done at 0, 6, and 12 weeks of treatment. Significance of differences between pre- and post-treatment values in each group was assessed using Student's paired t-test and between the groups using unpaired t-test. We found a drop in blood glucose, serum creatinine, blood urea, and 24 h total urinary protein levels and a rise in glomerular filtration rate, 24 h total urinary volume, and hemoglobin level in the treatment group compared to the control group.

Comparative evaluation of efficacy and safety profile of rhubarb and α-keto analogs of essential amino acids supplementation in patients with diabetic nephropathy.

To determine the efficacy and safety profile of rhubarb and α-keto analogs of essential amino acids supplementation in patients of diabetic nephropathy (DN), we studied 96 patients of DN attending a tertiary care center of the North India. The patients were randomly divided into three equal interventional groups. Group I (control) that received conservative management along with placebo, Group II (rhubarb) that received conservative management along with rhubarb capsule (350 mg, thrice daily), and Group III [keto amino acid (KAA)] that received conservative management along with α-keto analogs of essential amino acids (600 mg, thrice daily). The treatment was continued for 12 weeks. Clinical and biochemical parameters were assessed at 0, 4, 8, and 12 weeks of treatment. A progressive improvement in clinical features and biochemical parameters was seen in all three groups after 12 weeks of treatment. The KAA group showed more marked improvement in clinical features as well as biochemical parameters compared to the rhubarb group. There was a reduction in blood glucose, blood urea, serum creatinine, and 24 h total urine protein. There was an increase in hemoglobin, 24 h total urine volume, and glomerular filtration rate. There was no statistical difference between the rhubarb and KAA groups with respect to side effects (P > 0.05). Our study suggests that KAA is more effective than rhubarb as add-on therapy with conservative management in patients of DN.

Amelioration of cisplatin-induced nephrotoxicity by ethanolic extract of Bauhinia purpurea: An in vivo study in rats.

Our objective is to study the nephroprotective activity and antioxidant potential of Bauhinia purpurea unripe pods and bark against cisplatin-induced nephrotoxicity. Healthy adult albino rats of either sex (150-200 g) were randomly divided into six groups of six animals each Group I (vehicle control) and Group II (negative control). Group III (BBE200) and Group IV (BBE400) were administered the ethanolic extract of Bauhinia purpurea bark in doses of 200 and 400 mg/kg/day p.o., respectively, and Group V (BPE200) and Group VI (BPE400) were administered the ethanolic extract of Bauhinia purpurea unripe pods at doses of 200 and 400 mg/kg/day p.o., respectively. All the treatments were given for nine days. Cisplatin in a single dose of 6 mg/kg i.p. was given on the 4 th day to all groups, except the vehicle control group. On the 10 th day, blood and urine were collected for biochemical tests and the rats were sacrificed. The kidney was removed for histology and lipid peroxidation-antioxidant test. Cisplatin caused nephrotoxicity as evidenced by elevated blood urea, serum creatinine and urine glucose, and there was decreased creatinine clearance in Group II as compared with Group I. Administration of BBE and BPE at doses of 200 and 400 mg/kg in Group III and Group VI caused a dose-dependant reduction in the rise of blood urea, serum creatinine and urine glucose, and there was a dose-dependant increase in creatinine clearance compared with Group II. There was increased catalase and glutathione and decreased malondialdehyde levels in Group II, while BBE 400 (Group IV) and BPE 400 (Group VI) treatments significantly reversed the changes toward normal values. Histological examination of the kidney revealed protection in Group IV and Group VI compared with Group II. The ethanolic extract of Bauhinia purpurea unripe pods and bark has a nephroprotective activity against cisplatin-induced nephrotoxicity in rats.

Acute delirium in an elderly woman following zoledronate administration.

Zoledronate is a third-generation bisphosphonate having distinctive profile of high potency as well as prolonged duration of action. Intravenous zoledronate is the recently approved bisphosphonate for the treatment of osteoporosis and has an attractive once-yearly regimen for the treatment of osteoporosis. Here we report, for the first time, a case of acute delirium following zoledronate administration for osteoporosis. An 86-year-old female patient presented to orthopedics out-patient department (OPD) with complaints of pain and unable to bear weight on left thigh with history of fall from bed 2 months back. She was diagnosed as fracture neck of femur with severe osteoporosis and treated conservatively. She was given zoledronate IV 5 mg infusion over 30 min. After 10-12 h of zoledronate infusion, patient became confused, disorientated, and agitated. A septic work-up was negative. Electrolyte disturbances were excluded with normal sodium, potassium, calcium, and magnesium levels. Computed tomography of the brain was unremarkable. A metabolic cause could not be found for the change in her mental state. Patient was referred to medicine department where she was diagnosed as drug-induced acute delirium probably due to zoledronate. Patient was advised injections haloperidol and torsemide. In the following 48 h, her confusion got cleared and mental status was improved. According to the Naranjo's scale, the effect of zoledronate in our patient was scored 6 indicating a probable likelihood of causing delirium. It was a probable cause of acute delirium according to World Health Organization (WHO) causality scale.

Evaluation of Rhubarb Supplementation in Stages 3 and 4 of Chronic Kidney Disease: A Randomized Clinical Trial.

Objective. To evaluate the efficacy and safety of Rhubarb supplementation in patients of chronic kidney disease. Material and Methods. This study was a prospective comparative study conducted in patients of chronic kidney disease (stages 3 & 4) attending Renal Clinic of Department of Medicine, JN Medical College & Hospital, AMU, Aligarh. Patients were randomly divided into two interventional groups. Group I (Control) was given conservative management while Group II (Rhubarb) received conservative management along with Rhubarb capsule (350 mg, thrice daily) for 12 weeks. Haemogram and renal function tests were measured at 0, 4, 8, and 12 weeks of treatment. Results. There was progressive improvement in clinical features in both the groups after 12 weeks of treatment but Rhubarb group showed more marked improvement as compared to control group. Both groups showed gradual improvement in the biochemical parameters as compared to their pretreated values which was more marked in Rhubarb supplemented group. There was reduction in blood glucose, blood urea, serum creatinine, and 24 hour total urine protein (TUP). There was increase in haemoglobin, 24 hour total urine volume (TUV), and glomerular filtration rate (GFR). There was no statistical difference in two groups with respect to side effects (P > 0.05). Conclusion. Rhubarb supplementation improved the therapeutic effect of conservative management in stage 3 and stage 4 patients of chronic kidney disease.

Arctic-like rabies virus, Bangladesh.

Arctic/Arctic-like rabies virus group 2 spread into Bangladesh ≈32 years ago. Because rabies is endemic to and a major public health problem in this country, we characterized this virus group. Its glycoprotein has 3 potential N-glycosylation sites that affect viral pathogenesis. Diversity of rabies virus might have public health implications in Bangladesh.

Doxofylline and theophylline: a comparative clinical study.

OBJECTIVES: COPD is one of the major public health problems worldwide. Theophylline has been used in the treatment of COPD for decades. Doxofylline a new theophylline congener has been claimed to have better safety profile. The study was undertaken to compare theophylline and doxophylline at doses recommended and commonly used in clinical practice. METHODS: The study was conducted in patients of COPD in TB chest department of a medical college hospital. It was randomized, prospective and open label. A total of 154 patients were divided in two group .Group I was administered 400 mg theophylline SR once daily and group II was administered doxofylline 400 mg twice a day orally. Spirometric variables symptom score, and adverse effects were recorded on day 0, 7 and 21 of therapy. Data were compared and analysed using SPSS version 16. RESULTS: Results of the study showed that there was no statistically significant difference with respect to spirometric variables and symptom score in the two groups and there was no significant difference in two groups with respect to side effects (p>0.05). CONCLUSIONS: It is concluded that doxophylline has no advantage over theophylline in terms of either efficacy or safety on the doses commonly used in current clinical practice.

Treatment end point determinants for pulmonary tuberculosis: human resistin as a surrogate biomarker.

Treatment of tuberculosis (TB), which takes one human life every 15 s, globally, requires a prolonged (>6 months) antitubercular treatment (ATT) which, is known to have hepatotoxic side effects. This study was designed to explore the utility of human resistin, a proinflammatory hormone, as a sensitive biomarker to determine TB treatment end points. Patients for pulmonary tuberculosis enrolled under the directly observed treatment, short-course (DOTS) program were followed-up for six months and were monitored by sputum analysis, body weight and ELISA-based serum resistin and C-reactive protein (CRP) levels at 0, 2, 4 and 6 months, along with close family contacts of TB patients and healthy controls. The mean circulating resistin levels were found to be significantly higher (P < 0.001) in patients (n = 48, 25.74 ± 9.45 ng/ml) reporting for the first time for treatment (T0) as compared to healthy subjects (n = 45, 7.18 ± 2.40 ng/ml). Resistin levels in contacts (n = 48, 19.61 ± 7.88 ng/ml) also were found to be significantly (P < 0.001) elevated as compared to healthy controls. Significant increase in body weight after four months (P = 0.006) and at 6 months (P < 0.001) of treatment inversely correlated with resistin levels. Our data suggest resistin could be a surrogate marker for TB treatment in addition to its utility as an early prognostic biomarker for monitoring TB disease onset.

Effect of Nigella sativa oil on various clinical and biochemical parameters of insulin resistance syndrome.

AIM: The seeds of the Nigella sativa plant have been used to promote health and fight disease for centuries, especially in the Middle East and in Southeast Asia. This plant has been a focus of much research. This clinical study was undertaken to know the adjuvant effect of N. sativa oil on various clinical and biochemical parameters of the insulin resistance syndrome. MATERIALS AND METHODS: This prospective study was conducted at a tertiary health care center in North India. After confirmation of diagnosis, 60 patients who fulfilled the inclusion and exclusion criteria were enrolled in this study. Written informed consent was taken from all the patients enrolled. Approval from the institutional ethical committee was also obtained. The patients were divided into two groups of 30 each. In group I (the standard group), patients were advised tablet atorvastatin 10 mg once a day and tablet metformin 500 mg twice a day for a period of 6 weeks. In group II (the N. sativa group), the patients were advised tablet atorvastatin 10 mg once a day, tablet metformin 500 mg twice a day, and N. sativa oil 2.5 ml twice daily for a period of 6 weeks. Fasting and postprandial blood glucose, fasting lipid profile, and waist circumference were recorded before therapy and after completion of therapy. RESULT: The treatment group showed significant (P < 0.05) improvement with reference to total cholesterol, low density lipoprotein cholesterol (LDL-C), and fasting blood glucose (P < 0.05). CONCLUSION: N. sativa oil was found to be effective as an add-on therapy in patients of insulin resistance syndrome. N. sativa oil has a significant activity in diabetic and dyslipidemic patients.