Modulatory effect of Gymnema montanum leaf extract on brain antioxidant status and lipid peroxidation in diabetic rats

The effects of leaf extract from Gymnema montanum, an endangered and endemic plant, were examined on brain lipid peroxidation in experimental diabetic rats. Ethanolic extract of G. montanum leaves was administered orally (50, 100, and 200 mg/kg of body weight) for 3 weeks, and changes in blood glucose, plasma insulin, and lipid peroxidation markers such as thiobarbituric acid-reactive substances (TBARS), hydroperoxides, and levels of antioxidants, namely, superoxide dismutase, catalase, glutathione peroxidase, reduced glutathione, and glutathione-S-transferase, were examined in the brain of alloxan-induced diabetic rats. Glibenclamide was used as a standard reference drug. A significant increase in the activities of antioxidants was observed in brain on treatment with G. montanum leaf extract and glibenclamide for 3 weeks. Both the treated groups showed significant decreases in formation of TBARS and hydroperoxides in brain, suggesting a role in protective action against lipid peroxidation-mediated membrane damage. Our findings indicate that G. montanum leaf extract possesses antiperoxidative and antioxidant effects in addition to its antidiabetic activity. This report helps to create awareness on the need for conservation of medicinal plants, and G. montanum is one such plant that needs to be conserved through various propagation trials.     

Safety, tolerability, pharmacokinetics, and pharmacodynamics of an orally active novel camptothecin analog, DRF-1042, in refractory cancer patients in a phase I dose escalation study

The objective of this study was to characterize the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetics, and antitumor effects of DRF-1042, a novel camptothecin analog, in refractory solid tumor patients. DRF-1042 was given for 5 consecutive days for 2 weeks, repeated every 3 weeks at 1.5 to 270 mg/m(2). Adverse events were monitored following NCI-CTC. Pharmacokinetics of lactone and total forms were determined using validated high-performance liquid chromatography (HPLC) and noncompartmental methods. Efficacy was evaluated applying World Health Organization (WHO) criteria. The 1st course was used to determine DLT and MTD. Twenty-five patients received 73 courses of therapy. Myelosuppression and diarrhea were DLTs. MTD was 120 mg/m(2)/day. AUC increased approximately linearly with dose. The t(1/2) for lactone and total forms was 9.9 and 29 hours, respectively. AUCs correlated significantly with nadir leucopenia and grade 4 diarrhea. Two complete responses (CRs) and 2 partial responses (PRs) were observed. In addition, 4 stable diseases were observed. The recommended phase II dose is 80 mg/m(2)/day.     

Effect of vitamin D analog (1alpha hydroxy D5) immunoconjugated to Her-2 antibody on breast cancer

We previously showed that a new vitamin D analog, 1alpha(OH)D5 (D5), induced differentiation and inhibited the growth of breast cancer cells. In this report, we examined whether D5 specifically delivered to breast cancer cells could have any therapeutic effect. D5 was linked to Her-2 antibody using sulfosuccinimidyl 6-4 azido nitrophenylamido hexanode (SANPAH) as a linker. The Her-2 antibody selected in our study had no significant effect on the in vitro or in vivo growth of breast cancer cells; however, it had cell-differentiating action. In vitro, D5-Her-2 antibody conjugate (IMC) showed the ability to specifically bind to Her-2-expressing cells, to compete with Her-2 antibody for surface receptor and to cause internalization. IMC (equivalent to 5 microg Her-2 antibody given intraperitoneally once weekly for 6 weeks) significantly inhibited the growth of BT-474 cells transplanted into athymic mice. The in vivo growth-inhibitory effect of IMC treatment was similar to that observed in animals receiving D5 continuously as a dietary supplement. These results show that the targeted delivery of D5 by immunoconjugation to cell surface receptor antibodies may be of potential therapeutic value for the treatment of Her-2 positive breast cancer.     

Right atrial aneurysm in adults--report of three cases and review of literature

Right atrial aneurysm (RAA) or RA diverticula are described as saccular structures originating from the RA free wall. This must be differentiated from aneurysmal dilation of the entire right atrium. We diagnosed three cases of RAA since 2000. The first patient presented with effort intolerance, the second with recurrent palpitations, and the third was totally asymptomatic. In all the cases transthoracic echocardiography was definitive with little additional information obtained from catheterization. We report our experience and review the literature pertaining to adult presentation of this interesting pathology, of which only 20 cases have thus far been reported.     

Identification and characterization of a novel allosteric modulator (SoRI-6238) of the serotonin transporter

In the present study we describe a novel agent, SoRI-6238 (ethyl 5-amino-3-(3,4-dichlorophenyl)-1,2-dihydropyrido[3,4-b]pyrazin-7-ylcarbamate) that partially inhibits 5-HT transporter (SERT) binding and allosterically modulates SERT function. Membranes were prepared from rat brain. SoRI-6238 partially inhibited SERT binding to brain membranes with a plateau at about 40% of control. SoRI-6238 fully inhibited norepinephrine transporter (NET) and dopamine transporter (DAT) binding with IC(50) values of 12.1 microM and 5.8 microM, respectively. The apparent K(d) of [(125)I]RTI-55 binding to SERT increased, then reached a plateau with increasing concentrations of SoRI-6238. SoRI-6238 fully inhibited [(3)H]5-HT uptake, acting to decrease the V(max) (noncompetitive inhibition). In kinetic experiments, SoRI-6238 slowed the dissociation of [(125)I]RTI-55 from SERT and slowed the initial association rate. We conclude that SoRI-6238 partially inhibits SERT binding and function, most likely via an allosteric mechanism.     

Neodymium:yttrium-aluminum-garnet capsulotomy and intraocular pressure in pseudophakic patients with glaucoma

OBJECTIVE: To determine the 1- and 3-hour changes in intraocular pressure after neodymium:yttrium-aluminum-garnet (Nd:YAG) capsulotomy in pseudophakic patients with glaucoma and to determine the effect of acetazolamide and apraclonidine on these changes. DESIGN: Randomized controlled trial. PARTICIPANTS: Pseudophakic patients with glaucoma requiring Nd:YAG posterior capsulotomy (n = 76). INTERVENTION: Patients undergoing Nd:YAG posterior capsulotomy were randomly allocated to receive no therapy, oral acetazolamide (250 mg), or topical apraclonidine 1% within 1 hour before capsulotomy. MAIN OUTCOME MEASURES: Intraocular pressures 1 and 3 hours after laser therapy were recorded. RESULTS: Data were available for 76 eyes in 76 patients. Twenty-nine patients received no therapy; 24, oral acetazolamide; and 23, apraclonidine. One fifth (6/29) of patients with glaucoma developed a pressure rise of > or =5 mmHg if untreated, and 3% (1/29) developed a pressure rise of >10 mmHg. In comparison, no patients in the acetazolamide group developed a pressure rise of > or =5 mmHg (P = 0.02), and 1 of 24 in the apraclonidine group (P = 0.08) developed such a pressure rise, with none developing a pressure rise of >10 mmHg. When comparing all treated with nontreated, a reduction in the proportion with pressure rise was found (P = 0.01). All of the patients who developed a pressure rise of > or =5 mmHg did so within the first hour. CONCLUSIONS: In the absence of therapy, clinically significant post-Nd:YAG pressure rises occur in one fifth of patients with glaucoma undergoing capsulotomy. Oral acetazolamide and topical apraclonidine reduce the frequency and magnitude of pressure rises and are of comparable effectiveness. In this study, all clinically important pressure rises developed within the first hour.     

Ocular presentation of sphenoid mucocele

A sphenoid mucocele often presents late due to its deep-seated anatomical site. It has a varied presentation, due to its close relationship to the cavernous sinus and the base of the skull. It can present initially to the ophthalmologist with ocular complaints. In the present paper, the authors present two cases of sphenoid mucocele, one with an isolated third and one with an isolated sixth cranial nerve palsy.     

Detecting protein losing enteropathy by Tc-99m dextran scintigraphy: a novel experience

OBJECTIVE: To evaluate protien using enteropathy by Tc-99m dextran scintigraphy. METHODS: Methods for detecting protein loss from the intestine revolve around fecal nitrogen excretion, the clearance of alpha-1 antitrypsin in stools and by endoscopic biopsy. RESULT: The diagnosis of protein-losing enteropathy (PLE) can also be established by a scintigraphic method that is noninvasive, simple and requires no patient preparation or motivation. This diagnostic modality can also delineate the site of protein loss, thereby offering a targeted approach, and if need be, surgery. Radiolabelling of a non-protein, noncolloidal, nonparticulate and biofriendly molecule like dextran with Technetium-99m for imaging enteric protein loss was utilized in imaging eight children with PLE. CONCLUSION: The results were encouraging. The authors advocate the use of this diagnostic tool in identifying patients with PLE, particularly in the pediatric age group.