Development and characterization of in situ gel system for nasal insulin delivery.

The objective of the present study was to develop a thermosensitive in situ gel system based on chitosan and poly vinyl alcohol (PVA) for nasal delivery of insulin. The hydrogel was prepared by mixing chitosan and PVA. The concentration of the components was optimized during formulation development. The prepared hydrogel was characterized for gelation temperature, gelation time, viscosity changes, degree of swelling, in vitro release and in vivo hypoglycemic effect. The prepared hydrogel was liquid at room temperature while underwent thermal transition from solution below or at room temperature to non-flowing hydrogel when incubated at 37 degrees C for approximately 12 minutes with increased viscosity. The in vitro release of insulin from gel network was observed spectrophotometrically which was good enough to maintain blood glucose level for six hour. Furthermore, the formulation when evaluated for their in vivo hypoglycemic effect, demonstrated its ability to reduce glucose level. The observed in vitro and in vivo results indicate that the proposed thermosensitive in situ gelling system has substantial potential as nasal delivery system for insulin.

Dysplasia Epiphysealis Hemimelica (Trevor Disease) of the Patella: A Case Report.

CASE: We report a rare case of dysplasia epiphysealis hemimelica in an 11-year-old male child involving the patella. The patient noticed swelling in the right knee 6 months before presentation. On evaluation, there was a mass lesion originating from superior pole of the patella extending into the suprapatellar pouch. On opening the knee joint, it was found to be mainly cartilaginous in nature. Surgical excision of the mass was carried out. CONCLUSION: Trevor disease should be considered in the differential diagnosis of a mass originating from the patella in children. The recommended treatment is complete excision of the mass.

Targeted intracellular delivery of therapeutics: an overview.

During the last decade, intracellular drug delivery has become an emerging area of research in the medical and pharmaceutical field. Many therapeutic agents such as drugs and DNA/oligonucleotides can be delivered not just to the cell but also to a particular compartment of that cell to achieve better activity e.g. proapoptotic drugs to the mitochondria, antibiotics and enzymes to the lysosomes and various anticancer drugs and gene to the nucleus. The lipidic nature of biological membrans is the major obstacle to the intracellular delivery of macromolecular and ionic drugs. Additionally, after endocytosis, the lysosome, the major degradation compartment, needs to be avoided for better activity. To avoid these problems, various carriers have been investigated for efficient intracellular delivery, either by direct entry to cytoplasm or by escaping the endosomal compartment. These include cell penetrating peptides, and carrier systems such as liposomes, cationic lipids and polymers, polymeric nanoparticles, etc. Various properties of these carriers, including size, surface charge, composition and the presence of cell specific ligands, alter their efficacy and specificity towards particular cells. This review summarizes various aspects of targeted intracellular delivery of therapeutics including pathways, mechanisms and approaches. Various carrier constructs having potential for targeted intracellular delivery are also been discussed.

Monteggia fracture dislocation in a neonate resulting from birth trauma: a case report.

Birth-related injuries in an uncommon location may be missed initially and may result in significant morbidity. We report for the first time a case of a Monteggia fracture dislocation in a neonate resulting from birth trauma. The delayed presentation at 7 days made open reduction necessary in this otherwise nonoperatively managed injury because of the accelerated rate of bony union in infants. All high-risk births, including 2nd-born twins, should be thoroughly screened to avoid initial misdiagnosis.

Non-ionic surfactant based vesicles (niosomes) for non-invasive topical genetic immunization against hepatitis B.

DNA vaccines are capable of eliciting both humoral as well as cellular immune responses. Liposomes have been widely employed for DNA delivery through topical route; however, they suffer from certain drawbacks like higher cost and instability. In present study, non-ionic surfactant based vesicles (niosomes) for topical DNA delivery have been developed. DNA encoding hepatitis B surface antigen (HBsAg) was encapsulated in niosomes. Niosomes composed of span 85 and cholesterol as constitutive lipids were prepared by reverse phase evaporation method. Prepared niosomes were characterized for their size, shape and entrapment efficiency. The immune stimulating activity was studied by measuring serum anti-HBsAg titer and cyokines level (IL-2 and IFN-gamma) following topical application of niosomes in Balb/c mice and results were compared with naked DNA and liposomes encapsulated DNA applied topically as well as naked DNA and pure recombinant HBsAg administered intramuscularly. It was observed that topical niosomes elicited a comparable serum antibody titer and endogenous cytokines levels as compared to intramuscular recombinant HBsAg and topical liposomes. The study signifies the potential of niosomes as DNA vaccine carriers for effective topical immunization. The proposed system is simple, stable and cost effective compared to liposomes.

Intrapartum coccygeal fracture, a cause for postpartum coccydynia: a case report.

Coccydynia can result from a varying number of causes, parturition being one of them. Although strains and sprains of the ligaments attached to the coccyx have been thought to be the usual cause for coccydynia occurring after childbirth, an intrapartum coccygeal fracture dislocation can result in the same. A 28-year-old female presented to the orthopaedic department 4 weeks after the birth of her first child with the complaint of coccygeal pain. Examination revealed marked local tenderness over the coccyx but no crepitus was felt. Radiographs established the diagnosis of fracture and posterior dislocation between the second and third coccygeal fragments. Conservative treatment in the form of rest, doughnut ring, local heat, and avoidance of direct pressure over the area resulted in considerable improvement over the next 4 weeks. Coccygeal fracture dislocation may result in introital dyspareunia and tension myalgia of the pelvic floor. Pain from this lesion may become recurrently symptomatic. The diagnosis must be established at the outset and appropriate treatment instituted to avoid these complications.

Search for potential anticonvulsant agents. Synthesis of 2-phenyl/methyl-3-[o-, m- or p-(benzimidazol-2'-yl)phenyl]-6 or 6,8-substituted/unsubstituted quinazolin(3H)-4-ones.

Sixteen new quinazolones were synthesized by the condensation of substituted 4-oxo-3,1-benzoxazines and 2-(o-, m- or p-aminophenyl)benzimidazoles. All the sixteen compounds were tested for anticonvulsant activity in mice against pentylenetetrazole induced convulsions. Except for five compounds in which there was no protection, the others showed protection ranging from 20 to 80%.

Is PGL-1 also present in Leishmania donovani promastigotes?

A soluble antigen complex (SAC) derived from the ruptured promastigotes of Leishmania donovani parasites (LD-SAC) was used for complement fixation test (CFT) in leprosy Cases of tuberculoid and borderline tuberculoid leprosy, post-kala azar dermal leishmaniasis (TT, BT, PKDL) and control sera gave negative CFT. Smear-positive cases of borderline (BB, BL) and lepromatous (LL) leprosy and drug-resisting cases of pulmonary tuberculosis gave positive CFT; smear-negative cases of LL leprosy sera also gave positive CFT. Sera of smear-negative inactive LL patients contained only PGL-1 and PDIM antigens for a long time after they become inactive. Therefore, the positive CFT in inactive LL makes us suspect whether PGL-1 is present in LD promastigotes.

Anti-inflammatory and diuretic activity of a new class of compounds--Schiff bases of 3-amino-2-methylquinazolin 4(3H)-ones.

Eighteen Schiff Bases of 3-amino-2-methylquinazolin-4(3H)-ones were synthesised and screened for anti-inflammatory and diuretic activity. Anti-inflammatory activity was identified in PNG-1, PNG-13, PNG-14, PNG-15 and PNG-17.

Tuberculosis of the clavicle presenting as an expansile lytic lesion: a case report.

An unusual case of skeletal tuberculosis, presenting as an expansile osteolytic lesion in the lateral end of the clavicle is presented. Diagnostic confusion delayed appropriate medical therapy, leading to development of a discharging sinus with secondary infection, which further confused the picture. With re-emergence of tuberculosis as an important infection worldwide, and the ability of this disease to mimic many skeletal pathologies, this has to be included in the differential diagnosis, especially at unusual sites.

Renal transplantation across ABO barrier.

In India, patients without a compatible blood group donor are usually excluded from renal transplantation. For young patients, it is a difficult therapeutic choice to stay on long-term dialysis. We describe the case of a 19-year-old male patient who had blood group O +ve and had no compatible donor in the family. His mother was B +ve and was willing to donate. The patient had an initial anti-B antibody titer of 1:512 and underwent antibody depletion with plasmapheresis (11 sessions) and intravenous immunoglobulin (IVIG) 100 mg/kg after every plasmapheresis. He also received rituximab 500 mg for 3 days prior to transplant and was induced with basiliximab. At the time of transplant, his anti-B titers were <1:8. Post-operatively, he required four sessions of plasmapheresis and IVIG as his titers rebounded to 1:64. The titers then spontaneously subsided to <1:16 and have stayed at the same level for 6 months post-transplant. The patient continues to have normal renal function with a creatinine of 1.4 mg/dl% and has had no episodes of rejection.

Involvement of P-glycoprotein and CYP 3A4 in the enhancement of etoposide bioavailability by a piperine analogue.

Etoposide, a semi-synthetic derivative of podophyllotoxin, is widely used anticancer agent. Etoposide presents low bioavailability with wide inter-, and intra-patient variability after oral dosing. In an earlier study a piperine analogue, namely, 4-ethyl 5-(3, 4-methylenedioxyphenyl)-2E,4E-pentadienoic acid piperidide (PA-1), was shown to cause 2.32-fold enhancement of the absolute bioavailability of co-dosed etoposide in mice. In the present investigation a mechanistic evaluation was undertaken using various in vitro and animal-derived models. In everted rat gut sac studies PA-1 enhanced mucosal uptake of the drug while it inhibited efflux of Rh-123, a P-glycoprotein substrate from serosal-to-mucosal direction. In a single pass in situ perfusion experiment PA-1 significantly reduced the intestinal exsorption rate, exsorption clearance and the total plasma clearance of etoposide. On the other hand PA-1 did not alter the passive diffusion pattern of the drug in PAMPA assay. PA-1 was inhibitory to NADPH-assisted deethylation and demethylation reactions catalyzed by erythromycin N-demethylase, 7-methoxycoumarin-O-demethylase (MOCD) and ethoxyresorufin-O-deethylase (EROD). PA-1 was not cytotoxic to mucosal membrane and showed no adverse effect in acute toxicity determination. The results suggested that PA-1-mediated enhancement in the oral bioavailability of etoposide could possibly be due to its ability to modify P-gp/CYP 3A4 mediated drug disposition mechanisms.

Utility of C-2 (Cyclosporine) monitoring in postrenal transplant patients: A study in the Indian population.

The study was planned and conducted to assess the benefit of C-2 levels (blood cyclosporine levels two hours postdosing) monitoring over trough (C0) levels (predosing) in postrenal transplant patients. The patient population included 34 postrenal transplant individuals (28 males and six females, mean age of 39.9 +/- 12.3 years). The patients were first-transplant patients and were receiving a microemulsion form of cyclosporine A (CsA) as an immunosuppressant along with azathioprine and prednisolone. In addition, they were not on any enzyme inducer/inhibitor drugs, except for diltiazem. Timed collection of C0 and C-2 samples was done and the samples were immediately processed using the cedia cyclosporine plus assay kit. Estimation was done on a Beckman synchron CX5CE fully automated chemistry analyzer. Serum urea nitrogen and creatinine levels were checked. Poor graft survival was found in this population with 29.3% patients showing graft rejection. The graft rejection patients were assigned to two groups: group I with chronic graft rejection patients (17.6%) and group II with acute graft rejection patients (11.7%). Group III consisted of graft survival patients (70.7%). Mean +/- SD was calculated for C0 and C2 levels. Individual values for C0 and C-2 were plotted on a scatter chart. C0 and C-2 levels were normalized by calculating them as the percentage of their targets (data not shown) and compared using the Kruskal Wallis one-way analysis of variance. C0 levels in all the three groups were within the recommended therapeutic range (150-300 ng/mL) (P < 0.182). Blood C-2 concentrations did not achieve the recommended target levels in these patients. One-way analysis of variance for C-2 values when expressed as the percentage of the target values did not show any significant difference between these groups (P < 0.84). No significant difference was found in C0 levels between groups I, II, and group III patients when expressed as the percentage of the target values (P < 0.182). The mean serum urea nitrogen level was 26.4 +/- 8.1 mg/dL whereas the mean serum creatinine level was 1.79 +/- 0.8 mg/dL. As is evident in the present study, the target C2 levels of cyclosporine dosage were not achieved whereas the C0 levels in all the three groups were within the optimum therapeutic range. As the incidence of graft dysfunction was also proportionately high, the importance of C2 monitoring is further highlighted on the basis of this study The contributory factors for levels lower than the target levels, such as the use of low doses of cyclosporine and interacting drugs should be carefully monitored in clinical practice. The achievement of optimum levels of C-2 may help in reducing the higher incidence of graft rejection in these patients. This practice is of equal importance in reducing cyclosporine-related renal toxicity, a rather irreversible process.