Silatranes: a review on their synthesis, structure, reactivity and applications.

This critical review summarizes progress of the rapidly developing and very active field of silatrane chemistry. The first part of the review deals with general synthetic approaches used to synthesize different silatranes. The most interesting feature of silatranes, i.e., variation of Si-N bond length on the basis of the axial substituent of Si, and other structural features, are described in the second part with special emphasis on crystallographic and theoretical studies. It is followed by a discussion on the reactivity of various silatranes. Silatranes have now gained acceptance for a wide variety of applications which are summarized in the last section of review. Some of them have extensive interest due to their medical use to heal wounds or stimulate hair-growth (pilotropic activity), biological properties, pharmacological properties e.g. antitumor, anticancer, antibacterial, anti-inflammatory, fungicidal activity, stimulating effect in animal production and seed germination effects. The review focuses on the extended potential of silatranes in sol-gel processes, mesoporous zeotypes, atomic force microscopy, commercial products such as adhesion promoters, polymer formation and rubber compositions. This critical review will be helpful for general researchers, experts, advanced undergraduates and newcomers working on silatrane chemistry as this review presents greater emphasis on synthesis and characterization, structural properties, reactivity and applications of silatranes in the field of biology, material science, sol-gel chemistry, pharmaceutics, agriculture and medicine (311 references).

H-2-restricted helper factor secreted by clone hybridoma cells.

Biological and serological characteristics of a helper factor secreted by cloned hybridoma cells was described. The factor is carrier specific and contains determinants shared with immunoglobulin VH bu does not react with V kappa- or V lambda-specific antibodies. Presence of four H-2I-controlled antigenic specificities, Ia.ml, Ia.m2, Ia.17, and Ia.m7, was detected. Hence, it is possible that both A beta and E alpha loci may be involved in its control. Helper effect could be obtained only toward B cell sources that shared the H-2K and I-A antigens with the hybridoma cells. Similarly, the factor was absorbed only by spleen cells syngeneic in I-A. Previous studies have demonstrated that this clone binds antigen in an H-2-restricted manner. It follows that H-2-restricted helper cells produce H-2-restricted helper factors. Hence, they support the view that specific T cell factors may represent secreted T cell receptors.

Two separate genes regulate self-Ia and carrier recognition in H-2-restricted helper factors secreted by hybridoma cells.

H-2 heterologous T cell hybridomas were used to study the genetic control of dual, anti-nominal antigen and anti-self H-2 specificity of H-2 restricted T cell factors. Each of four hybridoma clones produced two helper factors. One was restricted for the Ia type of the normal T cell partner (H-2b), whereas the other was restricted for the ia type of the lymphoma partner (H-2k) of the somatic hybrid. This was shown by affinity separation on parental type spleen cells and on monoclonal anti-I-A-Sepharose. Both factors had carrier (chicken gamma globulin; CGG)-specific helper effect, and both bound to anti-VH-315-Sepharose. Because the lymphoma (BW-5147) partner could not contribute a CGG-specific locus, the H-2k-restricted, CGG-specific factor had to be the product of segregating anti-nominal and anti-self loci. This suggests that dual specificity is due to two independent loci and support the validity of dual recognition concepts. Anti-self specificity was associated with homologous Ia alloantigens in the individual factors. Therefore, Ia and anti-self might be linked. Implications of the major histocompatibility complex or VH nature of anti-self receptors and the relationship of T cell factors and receptors was discussed.

Differential turnover of enzymes involved in human monocyte eicosanoid metabolism. Selective inhibition of cyclooxygenase product formation by cycloheximide in the absence of effects on 5-lipoxygenase or phospholipase A2.

Human monocytes treated with cycloheximide (CHX) demonstrated a concentration- and time-dependent inhibition of prostaglandin E2 (PGE2) synthesis and release in response to stimulation with phorbol myristate acetate, ionomycin, serum-treated zymosan, or concanavalin A. The effect of CHX required preincubation and was largely reversible within 2 hr. Thromboxane A2 release was affected similarly but no comparable effects were observed on labeled arachidonic acid release or leukotriene B4 generation. The PGE2 response was also inhibited by CHX when monocytes were given exogenous arachidonic acid with or without stimulation. CHX pretreatment also comparably decreased the amount of immunoreactive cyclooxygenase in resting and stimulated monocytes. These data indicate that monocyte cyclooxygenase, in contrast to phospholipase A2 or 5-lipoxygenase and their regulatory proteins, turns over rapidly and may be a target for up- or down-regulation by pharmacologic or (potentially) physiologic agents which affect protein synthesis or degradation.

Involvement of central cholinoceptors in Metrazol-induced convulsions.

Atropine sulphate (10 mg/kg IP) afforded 90% protection against clonic convulsions induced by standard doses of metrazol (80 mg/kg SC) in mice, whereas atropine methonitrate (10 mg/kg IP) did not offer any protection. Furthermore, physostigmine (1 mg/kg IP) caused recurrence of convulsions in atropinzed metrazol-treated mice and converted the subconvulsive dose of metrazol (40 mg/kg SC) into a 100% convulsive dose. However, neostigmine (1 mg/kg IP) did not antagonize the protection afforded by atropine sulphate against metrazol. The results of the study suggest an involvement of central cholinergic mechanisms in metrazol-induced convulsions.

Transduction of a signal for arachidonic acid metabolism by untriggered CSF-1 receptor induces an opposite effect to that induced by CSF-1 receptor and its ligand: separate regulation of phospholipase A2 and cyclooxygenase by CSF-1 receptor/CSF-1.

The mouse hematopoietic cell line, 32D, was transfected with c-fms, which encodes for the CSF-1 receptor, a tyrosine kinase (TK). In the absence of CSF-1, transfected cells show moderate levels of arachidonic acid (AA) release and produce a substantial amount of prostaglandin E2 (PGE2) in comparison with the original cell line. Exposure of transfected cells to CSF-1, while inducing a substantial increase in arachidonate release, nevertheless resulted in inhibition of PGE2 production. Addition of ST638, a tyrosine kinase inhibitor, to cells transfected with c-fms in the absence of CSF-1 inhibited PGE2 production within 10-60 min. Its addition to the same cells in the presence of CSF-1 induced an opposite effect, but required longer treatment (24 h). In either cell type, AA release was not affected by this agent. These data indicate that CSF-1 may regulate cyclooxygenase activity. The different effect of CSF-1 receptor on PGE2 production in the presence or absence of CSF-1 and the opposite effect of a tyrosine kinase inhibitor on PGE2 suggest that both the receptor alone or the receptor-ligand complex may transduce an active, but different, signal through tyrosine phosphorylation. CSF-1 receptor and CSF-1 may exert separate, but related, effects on phospholipase A2 and cyclooxygenase activity which, in concert, or along with other tyrosine kinases, regulate prostaglandin production.

Catheter associated urinary tract infections in neurology and neurosurgical units.

OBJECTIVE: Catheter associated bacteriuria is the most common infection acquired in hospitals. The objective of the study was (1) to study the incidence of bacteriuria following indwelling urethral catheterization in patients with short-term vs long-term catheterization (2) to define the antibiotic resistance pattern among these isolates so that the study can provide guidelines for choosing an effective antibiotic against infections in catheterized patients. METHODS: This is a prospective study carried out over a period of 18 months in Neurology/Neurosurgical patients who had indwelling catheters for > or =48 h. RESULTS: In this study, 68 out of 800 (8.5%) adult inpatients acquired urinary tract infection following indwelling bladder catheterizations. The risk was significantly higher for female, elderly patients, critically ill and patients on prolonged catheterization. Among the bacterial pathogens, Escherichia coli was the commonest organism isolated (32.9%) followed by Pseudomonas sp. (15.1%) and Staphylococcus aureus (12.3%). Candida sp. comprised 13.7% of all isolates. Among Gram negative bacterial pathogens maximum number of isolates were sensitive to Amikacin (sensitivity of 42%). All Gram positive organisms were however sensitive to Vancomycin. CONCLUSIONS: Our results provide guidelines for choosing salvage therapy against hospital resistant strains causing infection in catheterized patients. However, antibiotics seem to prevent urinary tract infections but primarily in patients catherized for short duration, i.e. 3-14 days and not in patients with long-term catheterization.

Inhibition of release of arachidonic acid, superoxide, and IL-1 from human monocytes by monoclonal anti-HLA class II antibodies: effects at proximal and distal points of inositol phospholipid hydrolysis pathway.

Incubation of human elutriator-purified monocytes with anti-HLA-DR or DQ antibody inhibited the release of arachidonic acid induced by serum-treated zymosan (STZ), a phagocytic stimulus that is known to induce inositol phospholipid hydrolysis and Ca2+ influx. However, only anti-HLA-DR antibody partially inhibited STZ-induced inositol phospholipid hydrolysis and concanavalin-A-induced Ca2+ influx. Incubation with anti-HLA-DR or -DQ antibody inhibited phorbol ester-induced AA release as well as superoxide production and IL-1 release. Inhibition of monocyte function by anti-class II antibodies was not accompanied by cAMP elevation. Furthermore, addition of exogenous db-cAMP and other agents (forskolin, cholera toxin, or 3-isobutyl-1-methyl-xanthine) that increase cAMP levels through different mechanisms, alone or in combination with anti-HLA antibodies, had no inhibitory effect on factor release. Our results demonstrate that perturbation of class II molecules down-modulates cell activation at more than one point of the signal transduction pathway with dominant inhibition distal to inositol phospholipid hydrolysis. They also suggest that the inhibition by anti-HLA class II antibody is probably not mediated via cAMP elevation.

Bacteriology of burns.

A retrospective study was undertaken at University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi, to examine the bacterial isolates from the Burns unit and to determine the antibiograms of the isolates to commonly used antimicrobial agents. A total of 600 pus samples from as many patients received, over a period of 5 years (June 1993-June 1997) yielded 920) isolates. Pseudomonas spp. was the most common (36%) followed by Staphylococcus aureus (19%), Klebsiella spp. (15.54%), Proteus spp. (11.19%), Enterococcus faecalis (8.5%), Escherichia coli (5.10%), Acinetobacter spp. (1.1%), Salmonella senftenberg (0.8%) and other (3%). Pseudomonas spp. was the most susceptible to ceftazidime (83% susceptible) and cefoperazone (82% susceptible), whereas the drugs most effective in other Gram-negative organisms were amikacin, netilmicin and ciproflox. Vancomycin was effective in 100% of Gram-positive organisms. The infection of burn wounds with multiple organisms, with the superadded problem of drug resistance, necessitate the institution of a drug policy by the hospitals for burn patients.

Functional consequences of phospholipase A2 activation in human monocytes.

Human monocytes release arachidonic acid upon stimulation with a variety of soluble or particulate agents. These include: phorbol esters (i.e., 12-O-tetradecanoate phorbol-13-acetate, TPA), calcium ionophores (ionomycin), serum-treated zymosan (STZ) concanavalin A (Con A), and, to a minor degree, lipopolysaccharides (LPS). Protein Kinase C activation or increased intracellular Ca2+ are common features of the actions of most, if not all, of these stimuli. Prevention of PKC activation by the use of staurosporine or chelation of extracellular calcium by EGTA selectively impaired AA release, indicating that PLA2 may be regulated by either pathway concurrently. The generation of inositol phosphates and diacylglycerol by the action of phospholipase C, notably upon interaction with opsonized particles during phagocytosis, apparently constitutes the physiological correlate of stimulation via these agents. Release of arachidonic acid by the action of PLA2 or other phospholipid hydrolyzing enzymes leads directly to the formation of cyclooxygenase products. In the presence of markedly elevated calcium concentrations, 5-lipoxygenase (LO) is activated as well, leading to the formation and release of leukotrienes. Agents which stimulate AA release also initiate other monocyte functions, including generation of reactive oxygen intermediates and lymphokine release. This observation makes it tempting to implicate PLA2 activation in many aspects of monocyte physiology. However, no correlation with PLA2 activation and either superoxide or lymphokine release was found when multiple stimuli, including TPA, ionomycin, serum-treated zymosan, concanavalin A, or LPS, were compared simultaneously. Instead, our results indicate that PLA2 activation is regulated by the same mechanisms, including PKC activation and increased Ca2+, as are other enzymes which determine expression of monocyte function. Phospholipase A2 (PLA2) hydrolyzes fatty acid from the sn-2 position of a wide variety of phospholipids. Substrates for this (these) enzyme(s) include species which contain a variety of polar head groups (choline, serine, ethanolamine, etc.) and some phospholipids with either linkages in sn-1. In many cell types, including human monocytes, phospholipase A2 commonly acts on substrates containing arachidonic acid (AA). The liberation of free arachidonate is a first step in the metabolism of prostaglandins, hydroxyeicosatetraeinoic acids, (HETE'S), and leukotrienes (Lt's). Monocytes and macrophages have been shown to be rich sources of arachidonate and its metabolites. Some biologic properties of monocytes, notably their role as immunomodulating cells, have been attributed to eicosanoid production and release. Accordingly, much of the interest regarding PLA2 in human monocytes centers on this aspect of their function.(ABSTRACT TRUNCATED AT 400 WORDS)

[Acute tonsillitis: clinical symptoms; bacteriologic culture and rapid test as deciding criteria for the use of antibiotics]. / Akute Tonsillitis: Klinische Symptomatik; bakteriologische Kultur und Schnelltest als Entscheidungskriterien für Antibiotikaeinsatz.

In order to prevent late sequelae from an untreated streptococcal pharyngitis all patients with streptococcal tonsillitis/pharyngitis have to be treated with antibiotics, preferably penicillin. A correct diagnosis by clinical criteria is only achievable in 72% of patients with streptococcal pharyngitis. Additional criteria such as diagnosis by culture are, therefore, mandatory. Time is a major disadvantage of traditional culture methods. Slide agglutination tests show an acceptable sensitivity of 92% and a specificity of 93%. Due to the possibility of false negative test results, with consequent withholding of adequate antimicrobial chemotherapy, these test results should be used only as a valuable guide. Decision to administer an antibiotic should still be based on clinical criteria.

Frequency, microbial spectrum and outcome of spontaneous bacterial peritonitis in north India.

AIM: To determine the prevalence, microbial spectrum and outcome of spontaneous bacterial peritonitis (SBP) and its variants in hospitalized cirrhotics. STUDY DESIGN: Prospective cohort study at a tertiary referral center in North India. METHODS: Over a four-month period, 70 consecutive adult patients with decompensated cirrhosis were screened for the presence of SBP or its variants. Ascitic fluid culture was done by direct inoculation of blood culture bottles at the bedside. Blood, urine and other fluids were cultured during hospital stay when clinically indicated. Ascitic fluid total leukocyte count and culture were repeated at any time during hospital stay if the patient showed clinical signs of deterioration. Patients with SBP and culture-negative neutrocytic ascites (CNNA) were treated empirically on the basis of ascitic fluid leukocyte count. RESULTS: Twenty-one of 70 (30%) patients with cirrhosis were diagnosed to have SBP or its variants CNNA and monomicrobial bacterascites (MBA). Ninety-five percent of the patients who developed this complication were in Child-Pugh class C. A causative organism was isolated in 62% of these patients. Gram-negative bucilli accounted for 6 of 10 patients with SBP whereas all cases of MBA were due to infection with Gram-positive cocei. A third of patients with SBP/CNNA had evidence of extra-abdominal focus of infection with the same organism. All episodes of SBP/CNNA were initially treated with either ciprofloxacin (12 patients) or a combination of third generation cephalosporin, cefotaxime and an aminoglycoside, gentamicin (n = 6). Fourteen patients (67%) recovered whereas 6 patients died during hospital stay. CONCLUSION: SBP is a common complication of decompensated liver disease in North India and is associated with significant in-hospital mortality. Ciprofloxacin is an effective drug for initial treatment of SBP/CNNA. Synchronous extra-peritoneal focus of infection is a frequent occurrence in these patients.

Histoplasmosis of the liver: a rare case.

A 39 year old male presented with history of fever and jaundice for 3 months. A liver biopsy showed numerous ovoid fungal bodies around 5 mm in size in the macrophages and Kupffer cells. A diagnosis of hepatic histoplasmosis was made which is an uncommon entity in our country.

Effect of anxiolytics on blood sugar level in rabbits.

Anxiety disorders are more prevalent not only in normal individuals but also in diabetes mellitus. Diazepam, a benzodiazepine, and buspirone, an azaspirodecanedione, are the most often prescribed anxiolytics. Present study was aimed to investigate the effect of diazepam and buspirone on the blood sugar levels in rabbits. Buspirone (0.5 mg/kg/day p.o.) and diazepam (0.6 mg/kg/day p.o.) did not affect the glucose levels in rabbits even after one month of treatment. Present findings suggest that these two anxiolytics have minimal effect on blood sugar control.

Activity of third generation cephalosporins against Pseudomonas aeruginosa in high risk hospital units.

Ceftazidime and Cefoperazone are the two third generation cephalosporins with anti-pseudomonal activity. They have been frequently used in the I.C.U.s. in the developed countries but their use in the Indian hospitals has begun relatively recently. We studied the in-vitro susceptibility of 139 Pseudomonas aeruginosa isolates that were multiple drug resistant from the Resuscitation Unit/I.C.U. (61 strains), Burns Unit (48 strains), Surgical Post-operative unit (24 strains), Nephrology unit (6 strains) of our hospital to these two cephalosporine over a period of about 18 months. Antibiotic susceptibility was studied using Kirby Bauer's disc dibusion method. Out of a total of 139 strains of multiple drug resistant Pseudomonas aeruginosa tested, 17.9% were found resistant each to Ceftazidime and Cefoperazone separately and 10% were found resistant to both antibiotics.

A non-invasive model for measuring nociception after tooth pulp exposure.

Temporomandibular arthritis will lengthen a rodent's meal duration. We hypothesized that meal duration would also lengthen after tooth pulp exposure, suggesting that this behavior could be used to measure tooth nociception. To test this hypothesis, we placed rats in feeding units and subjected 4 anterior mandibular molars to pulp exposure, with and without pre-treatment with the analgesic buprenorphine-HCl. In the first study, male Sprague-Dawley rats were placed in computerized sound-attenuated feeding modules, the pulp of 4 molars on the mandible were exposed, and meal duration was measured for 13 days. In a second study, rats were injected with either the analgesic buprenorphine-HCl or saline every 12 hrs; injections were started one day before pulp exposure. Meal duration was determined before and after treatment. In the first study, pulp exposure significantly increased daily meal duration for 8 days. In the second study, pulp exposure lengthened daily meal duration, but the group that was treated with buprenorphine-HCl showed no significant difference compared with control rats without pulp exposure. Evidence supports that a lengthening in meal duration is a response to tooth nociception and that this nociception can be measured for over a week.

Reduced GABA(A) receptor α6 expression in the trigeminal ganglion alters inflammatory TMJ hypersensitivity.

Trigeminal ganglia neurons express the GABA(A) receptor subunit alpha 6 (Gabrα6) but the role of this particular subunit in orofacial hypersensitivity is unknown. In this report the function of Gabrα6 was tested by reducing its expression in the trigeminal ganglia and measuring the effect of this reduction on inflammatory temporomandibular joint (TMJ) hypersensitivity. Gabrα6 expression was reduced by infusing the trigeminal ganglia of male Sprague Dawley rats with small interfering RNA (siRNA) having homology to either the Gabrα6 gene (Gabrα6 siRNA) or no known gene (control siRNA). Sixty hours after siRNA infusion the rats received a bilateral TMJ injection of complete Freund's adjuvant to induce an inflammatory response. Hypersensitivity was then quantitated by measuring meal duration, which lengthens when hypersensitivity increases. Neuronal activity in the trigeminal ganglia was also measured by quantitating the amount of phosphorylated ERK. Rats in a different group that did not have TMJ inflammation had an electrode placed in the spinal cord at the level of C1 sixty hours after siRNA infusion to record extracellular electrical activity of neurons that responded to TMJ stimulation. Our results show that Gabrα6 was expressed in both neurons and satellite glia of the trigeminal ganglia and that Gabrα6 positive neurons within the trigeminal ganglia have afferents in the TMJ. Gabrα6 siRNA infusion reduced Gabrα6 gene expression by 30% and significantly lengthened meal duration in rats with TMJ inflammation. Gabrα6 siRNA infusion also significantly increased p-ERK expression in the trigeminal ganglia of rats with TMJ inflammation and increased electrical activity in the spinal cord of rats without TMJ inflammation. These results suggest that maintaining Gabrα6 expression was necessary to inhibit primary sensory afferents in the trigeminal pathway and reduce inflammatory orofacial nociception.