Genetic Polymorphism of Type 1 Intermediate Filament Wool Keratin Gene in Native Indian Sheep Breeds

Information is presented on the genetic polymorphism of the Type 1 intermediate filament wool keratin gene in 15 native Indian sheep breeds belonging to different agro-ecological regions of India. The study analyzed random blood samples of the 638 sheep by the PCR-RFLP technique. Restriction digestion analysis of a 480 bp PCR fragment of the first exon region with MspI revealed two allelic variants (M = 0.748 and N = 0.252) and three genotypes (MM = 0.543, MN = 0.410, and NN = 0.047) across the 15 sheep breeds. The allelic frequency differences for both alleles across the Indian breeds, irrespective of their geographic distribution, color pattern, and utility traits, were observed to be statistically insignificant by a chi-square test (P > 0.05). According to the pattern of occurrence of allelic variants (M > N), the Indian breeds exhibited similarity to some of the reported European sheep breeds. The average heterozygosity was 0.420, and none of the breeds deviated from Hardy-Weinberg equilibrium. The predominance of the M over the N allele supported its ancestry in Indian sheep too.     

Effects of 28-homobrassinolide on nickel uptake,protein content and antioxidative defence system in <Emphasis Type="Italic">Brassica juncea</Emphasis>

The effects of 28-homobrassinolide (HBL) on nickel uptake, protein content and activities of antioxidative enzymes were determined in the seedlings of Brassica juncea L. The seeds were treated with different concentrations (0, 0.01, 1 and 100 nM) of HBL for 8 h and then sown in the Petri plates containing various concentrations (0, 25, 50 and 100 mg dm⁻³) of nickel. After 7 d, observations were made on shoot and root length, Ni uptake, protein content and activities of antioxidative enzymes (guaiacol peroxidase, catalase, glutathione reductase, ascorbate peroxidase and superoxide dismutase). The growth of seedlings was inhibited by Ni, however, less after HBL pre-treatment. The protein content and antioxidative enzyme activities were also increased by HBL treatment.     

Effects of clenbuterol on contractility and Ca2+ homeostasis of isolated rat ventricular myocytes

Clenbuterol, a compound classified as a beta2-adrenoceptor (AR) agonist, has been employed in combination with left ventricular assist devices (LVADs) to treat patients with severe heart failure. Previous studies have shown that chronic administration of clenbuterol affects cardiac excitation-contraction coupling. However, the acute effects of clenbuterol and the signaling pathway involved remain undefined. We investigated the acute effects of clenbuterol on isolated ventricular myocyte sarcomere shortening, Ca2+ transients, and L-type Ca2+ current and compared these effects to two other clinically used beta2-AR agonists: fenoterol and salbutamol. Clenbuterol (30 microM) produced a negative inotropic response, whereas fenoterol showed a positive inotropic response. Salbutamol had no significant effects. Clenbuterol reduced Ca2+ transient amplitude and L-type Ca2+ current. Selective beta1-AR blockade did not affect the action of clenbuterol on sarcomere shortening but significantly reduced contractility in the presence of fenoterol and salbutamol (P < 0.05). Incubation with 2 microg/ml pertussis toxin significantly reduced the negative inotropic effects of 30 microM clenbuterol. In addition, overexpression of inhibitory G protein (Gi) by adenoviral transfection induced a stronger clenbuterol-mediated negative inotropic effect, suggesting the involvement of the Gi protein. We conclude that clenbuterol does not increase and, at high concentrations, significantly depresses contractility of isolated ventricular myocytes, an effect not seen with fenoterol or salbutamol. In its negative inotropism, clenbuterol predominantly acts through Gi, and the consequent downstream signaling pathways activation may explain the beneficial effects observed during chronic administration of clenbuterol in patients treated with LVADs.     

Contemporary strategies for the stabilization of peptides in the alpha-helical conformation

Herein we review contemporary synthetic and protein design strategies to stabilize the alpha-helical motif in short peptides and miniature proteins. Advances in organometallic catalyst design, specifically for the olefin metathesis reaction, enable the use of hydrocarbon bridges to either crosslink side chains of specific residues or mimic intramolecular hydrogen bonds with carbon-carbon bonds. The resulting hydrocarbon-stapled and hydrogen bond surrogate alpha-helices provide unique synthetic ligands for targeting biomolecules. In the protein design realm, several classes of miniature proteins that display stable helical domains have been engineered and manipulated with powerful in vitro selection technologies to yield libraries of sequences that retain their helical folds. Rational re-design of these scaffolds provide distinctive reagents for the modulation of protein-protein interactions.     

Comparative evaluation of nano-filled and conventional adhesives for bonding of molar tubes

It is of interest to compare the bonding characteristics of the two nano filled adhesives, Grandio (Voco, Cuxhaven, Germany) and Transbond Supreme LV (TSLV, 3M Unitek, Monrovia, California) with conventional bonding adhesive Transbond XT (TBXT, 3M Unitek) for bonding of molar tubes. 45 extracted human permanent molar teeth, divided into three groups of 15 each, were bonded with stainless steel molar tubes (3M Unitek, USA) using TBXT in Group 1, Grandio in Group 2, TSLV in Group 3. Remnant Index and shear bond strength was evaluated after 24 hrs. of storage with the aid of Instron Universal testing machine and Stereomicroscope respectively. Data were analysed using Analysis of Variance (ANOVA) test, Post-hoc Bonferroni test and Kruskal Wallis test. The mean SBS of Group 1(TBXT) was 13.86±3.27 MPa, Group 2 (Grandio) was 9.48±2.36 MPa and Group 3 (TSLV) was 11.64±2.71 MPa. Both nano-filled adhesives had SBS well above the clinically acceptable range. Assessment of ARI scores and type of bond failure revealed that adhesive failure for TBXT and TSLV and cohesive failure for Grandio. Nano-filled adhesives can be an appropriate substitute for the conventional adhesive for bonding of molar tubes.     

Down-regulation of NF-κB signalling by polyphenolic compounds prevents endotoxin-induced liver injury in a rat model

Activation of NF-κB has been reported to play a key role in causing endotoxin-induced hepatic damage through enhanced production of reactive oxygen species and pro-inflammatory mediators. In this context, the potential of polyphenolic phytochemicals in preventing endotoxin-induced liver damage remains unclear. Here, we demonstrate that catechin and quercetin have the potential to down-regulate the initial signalling molecule NF-κB which may further inhibit the downstream cascade including TNF-α and NO. These results were confirmed using N-nitro-L-arginine methyl ester (L-NAME), the inhibitor of inducible nitric oxide synthase (iNOS) along with the biochemical and histological alterations occurring in the presence and absence of supplementation with both the polyphenols. However, catechin was found to be more effective than quercetin against endotoxin-induced liver injury. These findings suggest that these polyphenols may form a pharmacological basis for designing a therapeutic agent against endotoxin-mediated oxidative damage.     

Synergistic effect of intrathecal fentanyl and bupivacaine in spinal anesthesia for cesarean section

BACKGROUND: Potentiating the effect of intrathecal local anesthetics by addition of intrathecal opiods for intra-abdominal surgeries is known. In this study by addition of fentanyl we tried to minimize the dose of bupivacaine, thereby reducing the side effects caused by higher doses of intrathecal bupivacaine in cesarean section. METHODS: Study was performed on 120 cesarean section parturients divided into six groups, identified as B8, B10 and B 12.5 8.10 and 12.5 mg of bupivacaine mg and FB8, FB10 and FB 12.5 received a combination of 12.5 mug intrathecal fentanyl respectively. The parameters taken into consideration were visceral pain, hemodynamic stability, intraoperative sedation, intraoperative and postoperative shivering, and postoperative pain. RESULTS: Onset of sensory block to T6 occurred faster with increasing bupivacaine doses in bupivacaine only groups and bupivacaine -fentanyl combination groups. Alone lower concentrations of bupivacaine could not complete removed the visceral pain. Blood pressure declined with the increasing concentration of Bupivacaine and Fentanyl. Incidence of nausea and shivering reduces significantly whereas, the postoperative pain relief and hemodynamics increased by adding fentanyl. Pruritis, maternal respiratory depression and changes in Apgar score of babies do not occur with fentanyl. CONCLUSION: Spinal anesthesia among the neuraxial blocks in obstetric patients needs strict dose calculations because minimal dose changes, complications and side effects arise, providing impetus for this study. Here the synergistic, potentiating effect of fentanyl (an opiod) on bupivacaine (a local anesthetic) in spinal anesthesia for cesarian section is presented, fentanyl is able to reduce the dose of bupivacaine and therefore its harmful effects.     

Floating drug delivery systems: A review

The purpose of writing this review on floating drug delivery systems (FDDS) was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. This review also summarizes the in vitro techniques, in vivo studies to evaluate the performance and application of floating systems, and applications of these systems. These systems are useful to several problems encountered during the development of a pharmaceutical dosage form. Published: October 19, 2005