Nanosuspension for improving the bioavailability of a poorly soluble drug and screening of stabilizing agents to inhibit crystal growth

The purpose of this study was to develop a nanosuspension of a poorly soluble drug by nanomilling process using wet media milling to achieve superior in vitro dissolution and high in vivo exposure in pharmacokinetic studies. A promising nanosuspension was developed with Vitamin E TPGS based formulation with particle size in the nano range. Although the formulation showed significant improvement during in vitro dissolution and in vivo plasma level, probably due to the strong hydrophobic interaction between Vitamin TPGS and the drug molecule, crystal growth was observed during stability studies. A systematic study was done with different combinations of solubilizer/stabilizer system in order to obtain a more stable nanosuspension. Hydroxypropyl methylcellulose (HPMC 3 cps) was found to stabilize the nanosuspension by better surface coverage due to stronger interaction with the drug as compared to other stabilizers used in this study.     

Tumor associated release of interleukin-10 alters the prolactin receptor and down-regulates prolactin responsiveness of immature cortical thymocytes

The soluble factors produced either by Ehrlich's ascites carcinoma (EAC) or thymic adherent cells (TAC) of tumor-bearing mice comprising of CD11b(+) and CD11c(+) antigen-presenting cells caused a sharp decrease in prolactin (PRL)-induced ConA-mediated effect on survival of PNA(+) thymocytes. Similar suppression of PRL-induced effect was observed when the cells were cocultured with TAC of EAC-bearing mice. Anti-IL-10 antibody could reverse the PRL inability to induce ConA-mediated effect on PNA(+) thymocyte survival, indicating the presence of IL-10 in EAC culture supernatant (EAC sup) and thymic microenvironment. IL-10 could block PRL-induced proliferation of PNA(+) thymocytes without affecting spontaneous apoptosis. IL-10 altered the expression of the long-form (LF) of PRL-R and reduced the PRL binding of the cells, suggesting down-regulation of the PRL effect on PNA(+) thymocyte by the cytokine. Induction of tumor, which was found to increase the IL-10 secretion by TAC, also modified the PRL-R (LF) to PRL-R (SF). Since PRL plays a role in survival, proliferation and differentiation of lymphoid progenitor cells, the tuning of PRL action by IL-10 may be a possible mechanism of depletion of immature cortical thymocytes and thymic atrophy in tumor-bearing mice.     

Media optimization studies for Serratiopeptidase production from Serratia marcescens ATCC 13880

Production of an anti-inflammatory enzyme serratiopeptidase by fermentation with Serratia marcescens ATCC 13880 was studied to ascertain optimal nutritional conditions for large scale production. To study biosynthesis and production of serratiopeptidase by Serratia marcescens ATCC 13880, different physicochemical parameters were studied and optimized. The optimized medium contain, (g/l) glycerine 10.0, maltose 10.0 as carbon source, peptone 10.0 as organic nitrogen source, ammonium sulphate 10.0 as inorganic nitrogen source, dihydrogen phosphate 10.0, sodium bicarbonate 10.0, sodium acetate 10.0 as inorganic salt source, ascorbic acid 10.0 as stabilizer, distilled water 1000 ml and the optimized fermentation conditions were pH 7.0, temperature 37 degrees C and duration 24 hr. The modified fermentation medium produced 27.36 IU/ml of serratiopeptidase compared to 17.97 IU/ml in basal medium and the molecular weight of the purified serratiopeptidase was found to be 52 kD.     

Our Experience of Anatomical Variations of Facial Nerve in Cadaveric Temporal Bone Dissection

Cadaveric dissections helps aspiring ear surgeon to learn anatomy of temporal bone so as to avoid injury to the many vital structures. Objectives are to study the course of facial nerve and its variation in 50 cases of temporal bone dissection. To study the various parameter of the tympanomastoid segments of facial nerve, its relation with the important middle ear structures and their variations. To study the incidence of anatomical variations such as dehiscence of bony canal of facial nerve, bony overhang in the oval window region. The Current study was conducted at Dept. of ENT Temporal bone lab. 50 temporal bones were dissected to study the various parameters of the tympano-mastoid segments of the facial nerve, its relations with the important middle ear structures and their anomalies. The present study was carried out from Jan 2016 to Jan 2019. Out of 50 bones dissected, 44 (88%) bones were well pneumatised and 6(12%) bones were sclerotic. Length of the tympanic segment varied from 7.8 to 11.88 mm with a mean of 9.47 mm (± 1.06 mm). In 17 bones (34%) length of the mastoid segment was 13.1–14 mm, in 12 bones (24%) the length was 14.1–15 mm, while in 10 bones (20%) it was 12–13 mm. In 6 bones (12%) it was 15.1–16 mm and < 12 mm in 5 other bones (10%). The distance of second genu from outer cortex varied from 17.87–23.67 mm with a mean of 19.64 mm (± 1.42 mm).Distance of chorda tympani from stylomastoid foramina varied from 3.4–7.8 mm with a mean of 5.69 mm (± 1.51 mm). The study has provided knowledge of anatomy of temporal bone and its pneumatization pattern, the anatomy of the facial nerve, its variations and their incidence, relation of various middle ear landmarks with the facial nerve and proficiency in dissection.     

Delay Of Insulin Addition To Oral Combination Therapy Despite Inadequate Glycemic Control

BACKGROUND Patients and providers may be reluctant to escalate to insulin therapy despite inadequate glycemic control. OBJECTIVES To determine the proportion of patients attaining and maintaining glycemic targets after initiating sulfonylurea and metformin oral combination therapy (SU/MET); to assess insulin initiation among patients failing SU/MET; and to estimate the glycemic burden incurred, stratified by whether HbA_1c goal was attained and maintained. DESIGN Longitudinal observational cohort study. SUBJECTS Type 2 diabetes patients, 3,891, who newly initiated SU/MET between 1 January 1996 and 31 December 2000. MEASUREMENTS Subjects were followed until insulin was added, health plan disenrolment, or until 31 December 2005. We calculated the number of months subjects continued SU/MET therapy alone, in total, and during periods of inadequate glycemic control; the A1C reached during those time periods; and total glycemic burden, defined as the estimated cumulative monthly difference between measured A1C and 8%. RESULTS During a mean follow-up of 54.6 ± 28.6 months, 41.9% of the subjects added insulin, and 11.8% received maximal doses of both oral agents. Over half of SU/MET patients attained but failed to maintain A1C of 8%, yet continued SU/MET therapy for an average of nearly 3 years, sustaining glycemic burden equivalent to nearly 32 months of A1C levels of 9%. Another 18% of patients never attained the 8% goal with SU/MET, yet continued that therapy for an average of 30 months, reaching mean A1C levels of 10%. CONCLUSIONS Despite inadequate glycemic control, a minority of patients added insulin or maximized oral agent doses, thus, incurring substantial glycemic burden on SU/MET. Additional studies are needed to examine the benefits of rapid titration to maximum doses and earlier initiation of insulin therapy. Supported by a research grant from Pfizer, Inc. Presented in poster form at the American Diabetes Association 66th Annual Meetings, June, 2006.     

Encountering Patient Suicide: A Resident's Experience.

OBJECTIVE: The authors reviewed the current literature for psychiatry residents' reactions to the suicide of a patient. This review also examines the responses of training programs to residents after such an incident. METHOD: Using Ovid Medline, the authors conducted a review of the scientific literature from 1966 to 2006, with search phrases consisting of: "patient suicide," "residency training programs," "psychiatry residents," and "therapists-in-training." RESULTS: There are a limited number of studies exploring residents' experiences following a patient suicide. Furthermore, only two studies examined the supportive measures that U.S. psychiatry training programs provide for residents afterwards. The few studies published suggest that the suicide of a patient is quite common during training and that residents undergo significant levels of psychological stress. Residency programs have yet to establish formal training and support systems to help trainees deal with these stressors. CONCLUSIONS: The findings from this review support further investigation into the effects of patient suicide on residents and the implementation of formal supports within psychiatry training.     

Association of early phase of colorectal carcinogenesis with STAT3 activation and its relevance in apoptosis regulation

Expression of STAT3/pSTAT3 in colorectal cancer (CRC) patients of Indian origin was studied to assess its significance in early detection and apoptosis regulation. Colorectal tissues with malignant lesions were STAT3/pSTAT3 positive in 66% of the cases and among these positive cases, well differentiated, moderately differentiated and poorly differentiated cancers were 86%, 60% and 0% respectively. All CRC specimens studied were immunoreactive with anti-carcinoembryonic antigen antibody. Cells purified from CRC tissues exhibited greater STAT3/pSTAT3 reactivity than peripheral blood mononuclear cells (PBMC) from healthy individuals, which served as control. apoptotic index (AI) was comparatively low in tissue specimens with STAT3/pSTAT3 expression. CRC cells with a comparatively less number of apoptotic cells, expressed a minimum number of Caspase-3 positive cells (4.73%), in comparison to healthy-PBMC (12.63%). CRC cells with high STAT3/pSTAT3 staining had cells with greater percentage of Bcl2 reactivity (23.05%), but less positivity with Caspase3 antibody (2.05%). Overall data suggests that CRC population was STAT3/pSTAT3 immunoreactive in a stage specific manner and STAT3 protects cancerous colorectal epithelial cells from apoptosis. Bcl-2, Cyclin D1 and Caspase-3 control the activity of apoptosis regulator, STAT3.     

Nonsurgical healing of large periradicular lesions using a triple antibiotic paste: A case series

The infection of the root canal system is considered to be a polymicrobial infection, consisting of both aerobic and anaerobic bacteria. Because of the complexity of the root canal infection, it is unlikely that any single antibiotic could result in effective sterilization of the canal. A combination of antibiotic drugs (metronidazole, ciprofloxacin, and minocycline) is used to eliminate target bacteria, which are possible sources of endodontic lesions. Three case reports describe the nonsurgical endodontic treatment of teeth with large periradicular lesions. A triple antibiotic paste was used for 3 months. After 3 months, teeth were asymptomatic and were obturated. The follow-up radiograph of all the three cases showed progressive healing of periradicular lesions. The results of these cases show that when most commonly used medicaments fail in eliminating the symptoms then a triple antibiotic paste can be used clinically in the treatment of teeth with large periradicular lesions.