Effects of traumatic brain injury on intestinal contractility.

BACKGROUND: Patients with traumatic brain injury (TBI) often suffer from gastrointestinal dysfunction including intolerance to enteral feedings. However, it is unclear how TBI affects small intestinal contractile activity. The purpose of this study was to determine if TBI affects intestinal smooth muscle function. METHODS: Sprague-Dawley rats were subjected to controlled cortical impact injury (TBI). Sham animals underwent a similar surgery but no injury (SHAM). Animals were sacrificed 1, 3, and 7 days after TBI and intestinal smooth muscle tissue was collected for measurement of contractile activity and transit, NF-kB activity, and cytokine levels. Brains were collected after sacrifice to determine volume loss due to injury. KEY RESULTS: Contractile activity decreased significantly in ileum, but not jejunum, in the TBI group 7 days after injury compared with SHAM. Brain volume loss increased significantly 7 days after injury compared with 3 days and correlated significantly with the contractile activity 1 day after injury. In the intestinal smooth muscle, NF-kB activity increased significantly in the TBI group 3 and 7 days after injury vs SHAM. Wet to dry weight ratio, indicating edema, also increased significantly in the TBI group. Interleukin-1α, -1ß, and -17 increased significantly in the TBI group compared with SHAM. CONCLUSIONS & INFERENCES: Traumatic brain injury causes a delayed but significant decrease in intestinal contractile activity in the ileum leading to delayed transit. The decreased intestinal contractile activity is attributed to secondary inflammatory injury as evidenced by increased NF-kB activity, increased edema, and increased inflammatory cytokines in the intestinal smooth muscle.

Hippo signalling controls Dronc activity to regulate organ size in Drosophila.

The Hippo pathway controls organ size by multiple mechanisms that ultimately regulate the transcriptional co-activator Yorkie (Yki). Downregulation of Hippo signalling leads to tissue overgrowths due to Yki-mediated activation of target genes, whereas overexpression of the pathway triggers apoptosis in developing tissues. However, the mechanism underlying cell death induced by Hippo (Hpo)-activation is not understood. We found that overexpression of Hpo leads to induction of Dronc (Drosophila Caspase-9 homologue) expression and downregulation of dronc can suppress/block Hpo-mediated apoptosis. Furthermore, upregulation of Dronc activity strongly suppressed the overgrowth caused by Yki overexpression thereby suggesting that Hippo signalling restricts Dronc activity. Hippo-mediated cell death requires the activity of the initiator caspase Dronc. Loss-of-function of dronc in genetic mosaics leads to cell survival and increased cell proliferation in imaginal discs. dronc is transcriptionally suppressed in Yki overexpressing cells or cells mutant for other Hippo pathway components like warts (wts). We propose that Dronc is a transcriptional target of the Hippo signalling pathway. The Hippo-Dronc connection has implications in control of overall organ size and other growth regulatory mechanisms like compensatory proliferation and cell competition.

Management of temporomandibular disorder associated with bruxism.

Bruxism is the non-functional clenching or grinding of the teeth that may occur during sleep or, less commonly in the daytime in 5-20% of adults and about 30% of 56 year old children. Although research on bruxism is extensive, its etiology remains debatable. There is some literature to suggest that bruxism is correlated with temporomandibular disorders (TMDs) and malocclusion. The aim of this article is to present the course of this condition in a case of bruxism coupled with TMD with special emphasis on the importance of accurate diagnosis of maxillofacial pain. We also report an association between supernumerary teeth and TMDs that has not been reported earlier in the literature.

Effect of glutaraldehyde and ferric sulfate on shear bond strength of adhesives to primary dentin.

AIM: The present study was undertaken to evaluate the effect of alternative pulpotomy agents such as glutaraldehyde and ferric sulfate on the shear bond strength of self-etch adhesive systems to dentin of primary teeth. MATERIALS AND METHODS: Eighty human primary molar teeth were sectioned in a mesiodistal direction and divided into experimental and control groups. Lingual dentin specimens in experimental groups were treated with glutaraldehyde and ferric sulfate. Buccal surfaces soaked in water served as control group. Each group was then divided into two groups based on the adhesive system used: Clearfil SE Bond and Adper Prompt L-Pop. A teflon mold was used to build the composite (Filtek Z-250) cylinders on the dentinal surface of all the specimens. Shear bond strength was tested for all the specimens with an Instron Universal Testing Machine. The failure mode analysis was performed with a Scanning Electron Microscope (SEM). RESULTS: The results revealed that glutaraldehyde and ferric sulfate significantly reduced the shear bond strength of the tested adhesive systems to primary dentin. Clearfil SE Bond showed much higher shear bond strength than Adper Prompt L Pop to primary dentin. SEM analysis revealed a predominant cohesive failure mode for both adhesive systems. CONCLUSION: This study revealed that the pulpotomy medicaments glutaraldehyde and ferric sulfate adversely affected the bonding of self-etch adhesive systems to primary dentin.

Fixed dose combinations for tuberculosis: Lessons learned from clinical, formulation and regulatory perspective.

Worldwide, tuberculosis (TB) remains one of the most important communicable diseases in terms of morbidity and mortality. Its control requires multi-drug therapy for at least six months, which could lead to patient non-compliance, failure of therapy and ultimately resulting in the emergence of drug resistance. Fixed dose combinations (FDCs) in TB therapy reduce the number of tablets to be consumed and thereby increase patient compliance with recommended treatment regimens. Thus, FDCs play a significant role in preventing the emergence of drug resistance and successful treatment. However, the quality of FDCs with respect to variable bioavailability and their registration requirements are major hurdles to their implementation in national TB control programs. It is anticipated that a large global market for FDCs will encourage large-scale production and increased competition, which in turn will result in FDCs at affordable prices. The Global Drug Facility (GDF), established by the World Health Organization (WHO), aims to ensure universal uninterrupted access to quality TB drugs for implementation of directly observed treatment short-course (DOTS) in resource-poor countries. In this program, four FDCs were accepted as the drugs of first choice because of their obvious advantages in controlling TB. This demands the necessity of addressing quality and registration requirements of FDCs systematically. In light of this current knowledge on anti-TB FDCs, their dosage, combinations, available clinical studies and the experiences with TB therapy has been discussed in this article, which should serve as lessons for selection of appropriate FDCs for other diseases such as malaria and AIDS.

Pharmacology of adenosine receptors in the vasculature.

Adenosine is widely distributed in mammals. One of the primary roles of adenosine within the cardiovascular system is to directly control the functions of both cardiac and vascular tissues. Recently, there has been considerable interest in the subclassification of adenosine receptors. Characterization of a heterogeneous population of receptors for adenosine could provide an opportunity for the development of novel compounds of therapeutic value. Adenosine is released from cells as a result of metabolism, and its release can be increased dramatically from cells that are metabolically stressed. This implies that adenosine can be released from a variety of cells throughout the body, as a result of increased metabolic rates, in concentrations that can have a profound impact on blood vessel function and, consequently, blood flow. It is recognized that the actions of this nucleoside on the vasculature are most prominent when oxygen demand is high and there is a reduction in oxygen tension at the site in question. Therefore, it is not surprising that adenosine has been shown to be an important regulator of blood vessel tone under hypoxic conditions. Furthermore, the activation of adenosine receptors on blood vessels can result in relaxation and/or contractions. The nature of the response subsequent to the activation of adenosine receptors is primarily dependent on the type of blood vessel involved and basal tone. This review will focus on the characterization of subtypes of adenosine receptors in blood vessels, as well as the effect of the stimulation of adenosine receptors on the peripheral circulation.

Axonal rejoining inhibits injury-induced long-term changes in Aplysia sensory neurons in vitro.

Injury of Aplysia sensory neurons, both in the CNS and in dissociated cell culture, produces long-term changes in these cells, among which are hyperexcitability and enhanced neuritic outgrowth (hypermorphogenesis). These long-term, injury-induced changes are attributable, in part, to the generation of new intrinsic cellular signals. Little is known, however, about the signals that maintain homeostasis within sensory neurons. To elucidate the role of homeostatic signals in Aplysia sensory neurons, we investigated how axonal rejoining alters the cellular consequences of axotomy. Sensory neurons in dissociated cell culture were axotomized. In some cases, the distal segment of the severed axon was then removed; in other cases, the proximal and distal segments of the severed axon were permitted to rejoin. If the severed distal segment was left unmolested, then axonal rejoining invariably occurred within 7 hr. Surprisingly, we found that the characteristic long-term cellular consequences of axotomy were suppressed by axonal rejoining. The long-term axotomy-induced changes were not inhibited merely by contact between the severed axon and another, uninjured sensory neuron. These results indicate that long-term changes in sensory neurons induced by injury are attributable, in part, to prolonged disruption of a retrograde homeostatic signal that originates in the distal segment of the growing neurite and chronically suppresses hyperexcitability and hypermorphogenesis.

Neurocysticercal serodiagnosis--updated.

For diagnosis of neurocysticercosis the gold standard would be a stereotactic biopsy and histological confirmation which are not universally available or acceptable to patients, hence the necessity of immunodiagnosis. The authors have narrated beautifully the serodiagnostic aspects of neurocysticercosis in its updated form and have discussed the subject with proper references.

Effect of iodine level in mustard (Brassica juncea) cake-based concentrate supplement on nutrient utilisation and serum thyroid hormones of goats.

To assess the influence of dietary iodine (I) supplementation on nutritional performance and serum thyroid hormones of goats, 12 adult Barbari goats (average weight 18.8kg) were assigned randomly to three dietary treatments. The goats were fed a mustard (Brassica juncea) cake containing concentrate supplement along with either 0mg (control, I(0)), 0.050mg (I(50)), or 0.075mg (I(75)) I per animal per day for 180 days. Oat hay was given ad libitum as basal roughage. There was no difference in intake and digestibility of various nutrients or N retention among the three groups in a metabolism trial after 90 days of experimental feeding. A second metabolism trial conducted at 165 days post-feeding revealed that daily intake of DM, DCP and ME were 39.9, 41.1 and 44.8g, 2.64, 3.01 and 2.97g, and 366, 414 and 415kJ per unit metabolic body size, respectively, for the I(0), I(50) and I(75) groups. Retention of N by goats was 1.75, 2.58 and 2.56g per day (P>0.05) for the three groups, but one of the control animal was in negative balance. Mean live weight of I(75) animals was higher (P<0.05) at the end of the experimental feeding period with net live weight gains of 2.6, 4.8 and 5.4kg for the three groups. Mean serum concentration of triiodothyronine was 1.20, 1.23 and 1.65ngml(-1), being significantly higher in I(75) group. Mean level of thyroxine was 18.3, 24.9 and 27.4ngml(-1), significantly (P<0.05) higher in both I-supplemented groups. It is concluded that supplementing I at the tested levels positively influenced the live weight gain of goats with no significant impact on the utilisation of nutrients. Serum thyroid hormones also increased in response to I supplementation.

Design and evaluation of microcapsules of diltiazem hydrochloride.

Diltiazem Hydrochloride (DTZ.HCl), a potent calcium channel blocker was microencapsulated by emulsion/solvent evaporation technique using non-aqueous solution of Ethylcellulose (EC) polymer to achieve its release from microcapsules at a slower rate. At the optimal conditions of process variables such as stirring speed, temperature of the medium, drug-polymer ratio, maximum encapsulation efficiency was obtained and the microcapsules produced were free flowing, discrete and spherical as evident from Scanning Electron Microscopy. The in vitro release experiments were carried out in the simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.2 phosphate buffer) using USP XXII apparatus II. The data obtained from the dissolution profiles were compared in the light of different kinetic models and the regression coefficients were compared.

Telepathology in India.

Telepathology is the most recent addition to the pathologist's diagnostic tools. It is the acquisition of macroscopic and microscopic images for electronic transmission for diagnosis, consultation and/or education. With the addition of the personal computer at the pathologist's desktop, the stage has been set for one of the greatest advantages the Internet has to offer. Telepathology in India is in infancy, and we at PathoIndia (www.Pathoindia.com) have started a series of publication images from interesting cases in the form of weekly quiz. After cases are published, hundreds of pathologists from around the world are invited by e-mail to send in their diagnosis and comments. The responses to this quiz suggest that telepathology is catching on in the pathology community. Another intention of this series is to identify and select qualified international and Indian pathologists who would be willing to help colleagues from India requesting second opinions online.

Preparation and biopharmaceutical evaluation of nitrofurantoin loaded Eudragit RS100 and Eudragit RL 100 micropellets.

The objective of the present investigation was to prepare nitrofurantoin micropellets coated with a combination of Eudragit RS 100 and Eudragit RL100 taken in varying ratios to achieve a sustained nitrofurantoin serum and urinary level over a prolonged period of time without any side effect. The method adopted was phase separation coacervation induced by non-solvent addition. The physical nature of the coating film was improved by a protective colloid, polyisobutylene (0% to 3% w/w). The optimized formulations were extensively evaluated for particle size analysis, Scanning Electron Microscopy, stability studies and finally in vitro and in vivo release studies and their statistical evaluation and correlation.

Design and biopharmaceutical evaluation of nitrofurantoin-loaded Eudragit RS100 micropellets.

Nitrofurantoin, a synthetic bactericidal drug, was encapsulated with Eudragit RS 100 polymer by a coacervation phase separation technique using variable proportions of polyisobutylene (0% to 3%) as a protective colloid. The micropellets were evaluated by scanning electron microscopy (SEM), particle size distribution, wall thickness, and loss of wall polymer were determined. The in vitro release experiments were carried out over the entire pH range of the gastrointestinal tract, the data obtained from the dissolution profiles were compared in the light of different kinetic models, and the regression coefficients were compared. The in vivo studies were performed on female human volunteers. A linear correlation was obtained from in vitro-in vivo studies.

Production of rat salivary cystatin S variant polypeptides in Escherichia coli.

Cystatins are protein inhibitors of papain and related cysteine proteinases. A series of continuous synthetic peptides corresponding to the entire sequence of rat salivary cystatin was used to localize the binding domains of the cystatin to papain. Several synthetic peptides, one from the aminoterminal sequence (peptide 1-24) and others from the carboxylterminal (peptides 66-79, 66-90, 79-90, 79-114), showed binding to papain, but none of the peptides showed inhibition of papain activity. Three recombinant rat salivary cystatin variants (N-terminal truncated protein lacking amino acid residues 1-9; variant 49-53, in which amino acid residues QVVAG of rat salivary cystatin had been replaced with amino acid residues LVL in mutant protein; and variant 65-78, in which amino acid residues 65-78 had been replaced with amino acids PG in mutant protein) were produced using the Escherichia coli expression system pGex-4T. To generate N-terminal truncated protein the desired coding region of the cystatin gene was amplified by polymerase chain reaction (PCR). To produce the variants 49-53 and 65-78, a PCR-based approach of gene splicing by overlap extension was used. Recombinant cystatin proteins were produced as insoluble inclusion bodies as fusion proteins with a glutathione S-transferase (GST) carrier. After solubilization with urea the GST carrier was cleaved from the fusion protein with thrombin and cystatin variants purified by fast liquid chromatography on a MonoQ column. The purified proteins reacted with antibodies to rat salivary cystatin. The N-terminal truncated and variant 49-53 exhibited very little inhibitory activity towards papain, whereas variant 65-78 exhibited papain-inhibitory activity similar to the full-length recombinant cystatin.

Long-term effects of axotomy on excitability and growth of isolated Aplysia sensory neurons in cell culture: potential role of cAMP.

Crushing nerves, which contain the axons of central sensory neurons, in Aplysia causes the neurons to become hyperexcitable and to sprout new processes. Previous experiments that examined the effects of axonal injury on Aplysia sensory neurons have been performed in the intact animal or in the semi-intact CNS of Aplysia. It therefore has been unclear to what extent the long-term neuronal consequences of injury are due to intrinsic or extrinsic cellular signals. To determine whether injury-induced changes in Aplysia sensory neurons are due to intrinsic or extrinsic signals, we have developed an in vitro model of axonal injury. Isolated central sensory neurons grown for 2 days in cell culture were axotomized. Approximately 24 h after axotomy, sensory neurons exhibited a greater excitability-reflected, in part, as a significant reduction in spike accommodation-and greater neuritic outgrowth than did control (unaxotomized) neurons. Rp diastereoisomer of the cyclic adenosine 3',5'-monophosphorothiate (Rp-cAMPS), an inhibitor of protein kinase A, blocked both the reduction in accommodation and increased neuritic outgrowth induced by axotomy. Rp-cAMPS also blocked similar, albeit smaller, alterations observed in control sensory neurons during the 24-h period of our experiments. These results indicate that axonal injury elevates cAMP levels within Aplysia sensory neurons, and that this elevation is directly responsible, in part, for the previously described long-term electrophysiological and morphological changes induced in Aplysia sensory neurons by nerve crush. In addition, the results indicate that control sensory neurons in culture are also undergoing injury-related electrophysiological and structural changes, probably due to cellular processes triggered when the neurons are axotomized during cell culturing. Finally, the results provide support for the idea that the cellular processes activated within Aplysia sensory neurons by injury, and those activated during long-term behavioral sensitization, overlap significantly.

Purification and characterization of rat parotid glycosylated, basic and acidic proline-rich proteins.

A unique family of proline-rich proteins (PRPs) is induced in rats following prolonged isoproterenol treatment. PRPs can be divided into glycosylated (GPRP), basic (BPRP) and acidic (APRP) proline-rich proteins based on their physicochemical characteristics. Inducible rat parotid PRPs were isolated from aqueous extracts of parotid glands of isoproterenol-treated animals by sequential chromatography on columns of DEAE-Sepharose CL-6B, Sephadex G-100 and FPLC on Suprose-12 column. The GPRP showed a single homogeneous band on sodium dodecylpolyacrylamide gel electrophoresis with an estimated molecular weight of approximately 220,000. Compositional analysis of GPRP revealed that this protein contained 19.7% glutamic acid/glutamine, 28.2% proline and 9.5% glycine, and 44% carbohydrate, consisting of fucose (2.81g/100g), mannose (9.78g/100g), galactose (9.29g/100g), N-acetylglucosamine (18.03g/100g) and N-acetylgalactosamine (3.90g/100g). Basic PRPs consisted of a family of proteins with estimated molecular masses ranging from 14-45 kDa. These proteins contained 42.6% proline, 20.65% glutamic acid/glutamine and 21.33% glycine. Acidic PRPs also comprised of a family of metachromatically stained ladder of 40-60 kDa containing 29.1% proline, 21.5% glutamic acid/glutamine and 17.8% glycine. APRP were heavily glycosylated containing N-acetylglucosamine (6.34g/100g), N-acetylgalactosamine (19.04g/100g) and glucuronic acid (38.08g/100g).

Effect of chlorine pollution on three fruit tree species at Ranoli near Baroda, India.

This paper describes the effect of chlorine pollution from an alkalies and chemical plant at Ranoli, near Baroda, on three tropical fruit tree species-Mangifera indica L. (mango) Manilkara hexandra Dubard. (rayan) and Syzygium cumini Skeels (Jamun). As compared to controls growing in a less polluted area, trees growing close to the plant showed reduced mean leaf area, a higher percentage of leaf area damaged, a reduction in fruit yield, chlorophyll pigments, protein and carbohydrate content, and higher accumulation of chloride in the foliar tissues. The accumulation of pollutaant, chloride, in the foliar tissues was very high in mango and jamun. Based on the degree of damage to the plants, the species studied were arranged in decreasing order of their sensitivity to chlorine pollution-mango, jamun and rayan.