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Background: A novel nanosomal paclitaxel lipid suspension (NPLS), free from Cremophor EL (CrEL) and ethanol, was developed to address the solvent-related toxicities associated with conventional paclitaxel formulation., Objective: To evaluate the efficacy and safety of NPLS versus CrEL-based paclitaxel (conventional paclitaxel) in patients with metastatic breast cancer (MBC)., Design: A prospective, open-label, randomized, multiple-dose, parallel, phase II/III study., Methods: Adult (18-65 years) female patients with MBC who had previously failed at least one line of chemotherapy were randomized (2:2:1) to NPLS 175 mg/m 2 every 3 weeks (Q3W, n  = 48, arm A), NPLS 80 mg/m 2 every week (QW, n  = 45, arm B) without premedication or conventional paclitaxel (Taxol ® , manufactured by Bristol-Myers Squibb, Princeton, NJ, USA) 175 mg/m 2 Q3W ( n  = 27, arm C) with premedication. In the extension study, an additional 54 patients were randomized (2:1) to arm A ( n  = 37) or arm C ( n  = 17)., Results: Pooled data from the primary study and its extension phase included 174 patients. The primary endpoint was the overall response rate (ORR). As per intent-to-treat analysis, ORR was significantly better in the NPLS QW arm as compared to conventional paclitaxel [44.4% (20/45) versus 22.7% (10/44), ( p  = 0.04)]. An improvement in ORR with NPLS Q3W versus conventional paclitaxel arm [29.4% (25/85) versus 22.7% (10/44)] ( p  = 0.53) was observed. Disease control rates observed were improved with NPLS Q3W versus conventional paclitaxel Q3W (77.7% versus 72.7%, p  = 0.66) and with NPLS QW versus conventional paclitaxel Q3W (84.4% versus 72.7%, p  = 0.20), although not significant. A lower incidence of grade III/IV peripheral sensory neuropathy, vomiting, and dyspnea was reported with NPLS Q3W versus conventional paclitaxel Q3W arms., Conclusion: NPLS demonstrated an improved tumor response rate and a favorable safety profile versus conventional paclitaxel. NPLS 80 mg/m 2 QW demonstrated a significantly better response versus conventional paclitaxel 175 mg/m 2 Q3W., Trial Registration: Clinical Trial Registry-India (CTRI), CTRI/2010/091/001344 Registered on: 18 October 2010 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MjEzNQ==&Enc=&userName=CTRI/2010/091/001344), CTRI/2015/07/006062 Registered on: 31 July 2015 (https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=MTE2Mjc=&Enc=&userName=CTRI/2015/07/006062)., Competing Interests: Dr Ateeq Ahmad, Dr Saifuddin Sheikh, Dr Shoukath M Ali, and Dr Imran Ahmad are employees of Jina Pharmaceuticals, Libertyville, IL, USA. Mr Ronak Patel is an employee of Lambda Therapeutic Research Limited, Ahmedabad India. Mr Mahesh Paithankar, Dr Lav Patel, Dr Anil Rajani, Dr Deepak Bunger, and Dr Alok Chaturvedi are employees of Intas Pharmaceuticals Limited, Ahmedabad, India., (© The Author(s), 2024.)

Vaginal yeast infection is one of the most common diseases caused by vulvovaginal candidiasis (VVC). Effective therapy for VVC is needed. A lipid-based amphotericin B gel 0.1% (LAB) was developed and evaluated for the treatment of VVC patients and those who failed to azole therapy. LAB was applied topically twice daily for 7 days to 64 moderate patients and 14 days to 55 severely infected VVC patients. Additionally, 66 patients who failed to azole therapy were treated twice daily with LAB for 14 days. A 91.5% clinical response and 93.16% mycological response was observed in VVC patients. The patients treated with LAB who failed to azole therapy showed a 75% clinical, 95.3% mycological response and 83% remission was observed.Overall, the LAB was found to be efficacious and safe for the treatment of VVC patients. Clinical Trial Registration All the trials were registered at Clinical Trial Registry of India (CTRI/2013/02/003378, CTRI/2014/02/004409)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: Antihyperglycemic activity of Thymoquinone (TQ) was evaluated in diabetic mouse model and patients., Methods: TQ (50 mg/kg) was orally administered daily for 21 days in combination with metformin in diabetic mice and a reduction on blood glucose level was monitored. In human, a 90-day randomized study was carried out in 60 Type 2 Diabetes mellitus patients to evaluate safety and efficacy of TQ administration with metformin in a 3-arm study. Patients in arm 1 (T1) received 1 tablet of metformin SR 1000 mg and 1 tablet of TQ 50 mg once daily. The second arm (T2) patients received 1 tablet of metformin SR 1000 mg and 2 tablets of TQ 50 mg once daily. Patients in arm 3 (R) received 1 tablet of metformin SR 1000 mg only., Results: The diabetic mice treated with combination of TQ and metformin showed significant decrease in blood sugar compared to those treated with only metformin. In patients who completed the study, the glycated hemoglobin (HbA1c) values in T1, T2 and R decreased after 3 months from 7.2, 7.2 and 7.3 to 6.7, 6.8, and 7.1, respectively. A greater reduction in Fasting Blood Glucose and Post Prandial Blood Glucose was also observed in T1 and T2 arms compared to R., Conclusion: At dose levels of 50 and 100 mg of TQ combined with a daily dose of 1000 mg Metformin demonstrated a reduction in the levels of HbA1c and blood glucose compared to the standard treatment of diabetic patients with metformin alone., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Aims and Objective: To assess the clinical features, complications and outcome in patients with central nervous system tuberculosis (CNS TB) and to correlate the clinical, laboratory and radiological findings of CNS TB., Materials and Methods: In a cross sectional study, total 50 diagnosed cases of CNS TB (either TB meningitis or tuberculoma) were studied. The data on demographic factors, clinical features, complications and laboratory findings, details of treatment and outcome were recorded and analyzed. Follow up was done during hospital stay and at the end of six months after completion of chemotherapy., Results: Out of 50, 42 patients had TBM (tuberculous meningitis) and 8 patients had tuberculoma. Mean age of patients was 33.5 yrs with male preponderance (M: F = 6.2:1), 66% patients had duration of symptoms more than 4 weeks. Common symptoms were fever (100%), headache (70%) and vomiting (64%). CSF staining for AFB was positive in 8% patients, mean CSF protein was 157 mg%, 32 patients had CSF lymphocytosis, (count >90%), CSF PCR was positive in 92.85%, CSF ADA levels were high (> 10 U/L) in 90.47%. On neuroimaging, 62 % patients had meningeal enhancement and 8 patients had tuberculomas. 10 patients were in stage I of disease, 24 in stage II and 16 in stage III. 30% mortality was observed, more in HIV positive patients with stage III disease. On followed up after 6 months of discharged patients (n=35), 10 patients had full recovery and 17 had recovery with neurological deficit, however 8 patients lost follow up., Conclusion: Diagnosis of CNS TB should be based on clinical features and 3 or more supportive criteria rather than CSF positivity on staining or culture. Rapid and early diagnosis by positive CSF PCR and CT/MRI findings should replace CSF AFB staining and culture in further for the diagnosis of CNS TB., (© Journal of the Association of Physicians of India 2011.)

Background: Nanosomal docetaxel lipid suspension formulation was developed to eliminate ethanol and polysorbate 80 from the currently used docetaxel (Taxotere) drug for treatment of cancer patients. NDLS clinical safety and efficacy was evaluated and compared with Taxotere at 75 mg/m(2) in metastatic breast cancer patients., Patients and Methods: A total of 72 patients were randomized in a ratio of 2:1 (NDLS:Taxotere). Patients treated with NDLS were not premedicated with corticosteroids as required with solvent-based Taxotere. Disease status and tumor response was assessed after every 2 cycles of treatment using Response Evaluation Criteria in Solid Tumors 1.1 guidelines through cycle 6., Results: Overall therapeutic response (complete + partial) rate in metastatic breast cancer patients treated with NDLS and Taxotere were 35.5% and 26.3%, respectively, indicating better response in patients treated with NDLS. Patients in the NDLS group were not premedicated but the safety results of NDLS were found to be comparable with Taxotere., Conclusion: NDLS formulation with no premedication provides an alternative treatment option for breast cancer patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Amphotericin B was formulated in lipids (Nanosomal Amphotericin B) without using any detergent or toxic organic solvents during the preparation. Electron microscopy and particle size determination of Nanosomal Amphotericin B showed a homogeneous population of nanosized particles below 100 nm. Hemolysis assay indicated that Nanosomal Amphotericin B causes significantly less lysis of red blood cells than Amphotericin B deoxycholate and was comparable to Ambisome. A maximum daily dose of Nanosomal Amphotericin B at 5 mg/kg in rabbits and 10 mg/kg in mice for 28 days showed no symptoms of toxicity, mortality or significant body weight reduction. Hematological and gross pathological analysis of tissues revealed no abnormalities attributable to the drug treatment. Nanosomal Amphotericin B and Ambisome were injected (iv) at 2 mg/kg consecutively for 5 days into mice infected with Aspergillus fumigatus. The treatment resulted in 90% survival with Nanosomal Amphotericin B and only 30% survival with Ambisome after 10 days of fungal infection. However, all of the 10 control mice which were not treated with Amphotericin B died within 5 days of fungal infection. Nanosomal Amphotericin B is safe, cost effective and provides an alternative option for treatment of fungal disease., (Copyright 2010 Elsevier B.V. All rights reserved.)

Objective: Develop Nanosomal formulation of Tacrolimus to provide safer alternative treatment for organ transplantation patients. Investigate safety, tolerability and pharmacokinetics of Nanosomal Tacrolimus formulation versus marketed Tacrolimus containing polyoxyl 60 hydrogenated castor oil (HCO-60) that causes side effects., Methods: Nanosomal Tacrolimus was prepared in an aqueous system. The particle size was measured by Particle Sizing Systems and structure morphology was determined by freeze-fracture electron microscopy. Investigational safety studies were conducted in mice and rats. Safety and pharmacokinetics of Nanosomal Tacrolimus were also evaluated in healthy human subjects., Results: The morphology of Nanosomal Tacrolimus showed a homogeneous population of nanosized particles with mean particle size of less than 100 nm. A 14 day consecutive administration of Nanosomal Tacrolimus up to 5 and 10mg/kg dose in rats and mice respectively, resulted in no mortality. Nanosomal Tacrolimus in human studies showed that it is safe and the pharmacokinetics profile is similar to the marketed HCO-60 based Tacrolimus. No significant change in peripheral blood lymphocyte percentage was noted in either mice or healthy human male subjects., Conclusions: Nanosomal Tacrolimus is well characterized product which provides a new treatment option. It contains no alcohol or surfactants like HCO-60. Thus, Nanosomal Tacrolimus presents a new and improved therapeutic approach for organ transplant patients compared to the marketed HCO-60 based Tacrolimus product., (Copyright 2009 Elsevier B.V. All rights reserved.)

Functional outcome at three months was studied in 72 patients with ischemic stroke. The Canadian Neurological Scale was used to assess the severity of stroke at admission and functional outcome at 3 months was assessed using modified Rankin scale. The size and site of the infarct was noted from the initial CT. Risk factors like hypertension, diabetes, and serum cholesterol were analyzed. Initial neurological scoring at admission, and size and site of the infarct were significantly associated with functional recovery at 3 months.

The authors report a patient with the rare presentation of bilateral external jugular vein thrombosis. A 45-year-old man presented with swelling over both sides of the neck and puffiness of the face. Physical examination revealed cordlike thickening of both the external jugular veins. Two-dimensional echocardiographic and Doppler studies showed thrombosis of both the external jugular veins and digital subtraction angiography (DSA) revealed nonvisualization of external jugular veins of either side. No malignancy, coagulation disorder, or any infection was demonstrable. A regular follow-up for 1 year was done, but no other cause could be found and there was no progression of the disease.