Ciprofloxacin in the prevention and treatment of surgical infections]

A clinico-laboratory study on ciprofloxacin made by Bayer (Germany) was applied to patients with extended posttraumatic wounds and performed with the aim of preventing postoperative purulent complications in patients operated on the organs of the gastrointestinal tract. In the both groups ciprofloxacin was administered orally in doses of 500 and 1000 mg and intravenously in a dose of 200 mg. The results of the assay on ciprofloxacin sensitivity of the isolates from the wound excretion and urine showed that they were more sensitive to ciprofloxacin than to aminoglycosides and cephalosporins. 15 minutes after the intravenous administration the serum concentration of ciprofloxacin amounted to 7.5 +/- 0.9 micrograms/ml and in 6 hours it was equal to 0.45 +/- 0.45 micrograms/ml, the mean concentrations of ciprofloxacin being attained in the bile (8.7 +/- +/- 3.9 micrograms/ml), gallbladder wall (5.5 +/- 3.8 micrograms/g), liver (0.73 micrograms/g), muscles (1.93 micrograms/g) and tendon (0.15 microgram/g). After the oral administration in a dose of 500 mg ciprofloxacin was detected in the blood serum in an amount of 2.0 +/- 0.7 micrograms/ml in 1 hour and in an amount of 0.9 +/- 0.13 micrograms/ml in 6 hours. After the drug oral administration in a dose of 1000 mg the maximum concentrations were: 6.34 +/- 4.2 micrograms/ml on the average and 2.1 +/- 0.8 micrograms/ml in 6 hours (0.4 micrograms/g in the muscles, 1.4 micrograms/g in the skin and 0.34 micrograms/g in the bones). The study showed that ciprofloxacin was a highly efficient antimicrobial agent in the treatment of the complicated wound infections and the prophylaxis of the purulent complications during the postoperative period in the patients operated on gastrointestinal organs.     

Preclinical investigation and standardization of metronidazole soft dosage forms]

Comparative acute and subacute toxicity of Dentamet gel and Metrovagin suppositories manufactured by ZAO Altaivitaminy was studied with using analogous drugs, i. e. Metrogil Denta, a gel for the gingivae, manufactured by Unique Pharmaceutical Laboratories (India), and Flagil manufactured by Haupt Farma Livron (France) as the reference drugs. It was shown that the drugs induced no changes in the exterior, hair state, body weight and mobility of the experimental animals vs. the control. The pharmacokinetic study of Metrovagin vaginal suppositories vs. the registered analogous drug Flagil showed that Metrovagin was bioequivalent to Flagil. The relative bioavailability of the new drug vs. the control was 103.13%.     

The antidepressant-like effect of Ocimum basilicum in an animal model of depression

We investigated the efficacy of Ocimum basilicum (OB) essential oils for treating depression related behavioral, biochemical and histopathological changes caused by exposure to chronic unpredictable mild stress (CUMS) in mice and to explore the mechanism underlying the pathology. Male albino mice were divided into four groups: controls; CUMS; CUMS plus fluoxetine, the antidepressant administered for pharmacological validation of OB; and CUMS plus OB. Behavioral tests included the forced swim test (FST), elevated plus-maze (EPM) and the open ?eld test (OFT); these tests were performed at the end of the experiment. We assessed serum corticosterone level, protein, gene and immunoexpression of brain-derived neurotropic factor (BDNF) and glucocorticoid receptors (GRs) as well as immunoexpression of glial fibrillary acidic protein (GFAP), Ki67, caspase-3 in the hippocampus. CUMS caused depression in the mice as evidenced by prolonged immobility in the FST, prolonged time spent in the open arms during the EPM test and reduction of open field activity in the OFT. OB ameliorated the CUMS induced depressive status. OB significantly reduced the corticosterone level and up-regulated protein and gene expressions of BDNF and GR. OB reduced CUMS induced hippocampal neuron atrophy and apoptosis, and increased the number of the astrocytes and new nerve cells. OB significantly increased GFAP-positive cells as well as BDNF and GR immunoexpression in the hippocampus.     

The Phosphatidylinositol Transfer Protein Domain of Drosophila Retinal Degeneration B Protein Is Essential for Photoreceptor Cell Survival and Recovery from Light Stimulation

The Drosophila retinal degeneration B (rdgB) gene encodes an integral membrane protein involved in phototransduction and prevention of retinal degeneration. RdgB represents a nonclassical phosphatidylinositol transfer protein (PITP) as all other known PITPs are soluble polypeptides. Our data demonstrate roles for RdgB in proper termination of the phototransduction light response and dark recovery of the photoreceptor cells. Expression of RdgB''s PITP domain as a soluble protein (RdgB-PITP) in rdgB² mutant flies is sufficient to completely restore the wild-type electrophysiological light response and prevent the degeneration. However, introduction of the T59E mutation, which does not affect RdgB-PITP''s phosphatidylinositol (PI) and phosphatidycholine (PC) transfer in vitro, into the soluble (RdgB-PITP-T59E) or full-length (RdgB-T59E) proteins eliminated rescue of retinal degeneration in rdgB² flies, while the light response was partially maintained. Substitution of the rat brain PITPα, a classical PI transfer protein, for RdgB''s PITP domain (PITPα or PITPα-RdgB chimeric protein) neither restored the light response nor maintained retinal integrity when expressed in rdgB² flies. Therefore, the complete repertoire of essential RdgB functions resides in RdgB''s PITP domain, but other PITPs possessing PI and/or PC transfer activity in vitro cannot supplant RdgB function in vivo. Expression of either RdgB-T59E or PITPα-RdgB in rdgB ⁺ flies produced a dominant retinal degeneration phenotype. Whereas RdgB-T59E functioned in a dominant manner to significantly reduce steady-state levels of rhodopsin, PITPα-RdgB was defective in the ability to recover from prolonged light stimulation and caused photoreceptor degeneration through an unknown mechanism. This in vivo analysis of PITP function in a metazoan system provides further insights into the links between PITP dysfunction and an inherited disease in a higher eukaryote.The Drosophila retinal degeneration B protein (RdgB)¹ plays a critical role in the fly photoreceptor cell. The rdgB mutant phenotype is characterized by retinal degeneration whose onset, while discernible in dark-reared flies, is greatly accelerated by raising the flies in light (Harris and Stark, 1977; Stark et al., 1983). Typically, rdgB mutant flies begin to exhibit the morphological hallmarks of photoreceptor cell degeneration several days after eclosion (Harris and Stark, 1977; Stark et al., 1983). In addition, these mutant flies exhibit an abnormal light response, as recorded by the rapid deterioration of the electroretinogram (ERG), shortly after the fly''s initial exposure to light. This ERG defect is manifested before any obvious physical signs of retinal degeneration (Harris and Stark, 1977), which suggests that the defect in the light response may precipitate the course of retinal degeneration.In the photoreceptor cell, RdgB localizes to both the axon and the subrhabdomeric cisternae (SRC) (Vihtelic et al., 1993; Suzuki and Hirosawa, 1994). The SRC is an extension of the endoplasmic reticulum that functions both as an intracellular Ca²⁺ store and a compartment through which rhodopsin traffics en route to the rhabdomere (Walz, 1982; Matsumoto-Suzuki et al., 1989; Suzuki and Hiosawa, 1991). Thus, RdgB is the first identified protein required for visual transduction that is not localized in the photoreceptor rhabdomere. Genetic epistasis analyses suggest RdgB functions downstream of both rhodopsin and phospholipase C (PLC) in the visual transduction cascade as both the ninaE (encoding the opsin expressed in photoreceptor cells R1-6 [O''Tousa et al., 1985; Zuker et al., 1985]) and norpA (encoding phospholipase C [Bloomquist et al., 1988]) mutations suppress the rdgB-dependent, light-enhanced retinal degeneration (Harris and Stark, 1977; Stark et al., 1983). Consistent with this view, constitutive activation of the Drosophila G protein transducin analogue (DGq), either by application of nonhydrolyzable GTP analogues or by expression of a constitutively activated Gα subunit (Dgq1), effects a rapid degeneration of rdgB retinas in the absence of light (Rubinstein et al., 1989; Lee et al., 1994). RdgB apparently functions downstream of the inaC-encoded protein kinase C (PKC) because: (a) application of phorbol ester to rdgB mutant retinas, which presumably activates the inaC-encoded PKC, stimulates retinal degeneration in the absence of light (Minke et al., 1990); and (b) the rdgB retinal degeneration is weakly suppressed by the inaC mutation (Smith et al., 1991). Thus, the available evidence identifies an execution point for RdgB downstream of PKC in the visual transduction cascade.RdgB is a 116-kD membrane polypeptide with six potential transmembrane domains (Vihtelic et al., 1991). Additionally, the amino-terminal 281 RdgB residues share 42% amino acid identity with the rat brain phosphatidylinositol (PI) transfer protein α isoform (PITPα) (Vihtelic et al., 1993). Whereas PITPs are operationally defined by their ability to catalyze the transfer of either PI or phosphatidylcholine (PC) monomers between membrane bilayers in vitro (Bankaitis et al., 1990; Cleves et al., 1991; Wirtz, 1991), how the phospholipid transfer activity pertains to in vivo function is less clear. The yeast PITP (Sec14p) uses its PI and PC binding activities in two independent, yet complementary, ways that serve to preserve a Golgi pool of diacylglycerol that is critical for the biogenesis of Golgi-derived secretory vesicles (Kearns et al., 1997). Reconstitution studies suggest that mammalian PITPs play important roles in PLC-mediated inositol signaling, ATP-dependent, Ca²⁺-activated secretion, and constitutive secretion from the trans-Golgi network (Hay and Martin, 1993, 1995; Thomas et al., 1993, 1995; Ohashi et al., 1995). However, because the PITP requirement for these processes is generally satisfied by any PITP (even those lacking any primary sequence identity), the physiological relevance of these PITP involvements remains to be determined (Skinner et al., 1993; Cunningham et al., 1995; Ohashi et al., 1995; Alb et al., 1996). The recent finding that the mouse vibrator mutation represents a hypomorphic mutation in the pitpn gene, which encodes PITPα, indicates that PITP function is important to neuronal function (Hamilton et al., 1997). RdgB''s PITP domain (when expressed as a soluble protein in Escherichia coli) is able to effect intermembrane transfer of PI in vitro (Vihtelic et al., 1993). Unlike all previously characterized PITPs, which are 32–35-kD soluble proteins (Bankaitis et al., 1989; Cleves et al., 1991; Wirtz, 1991), RdgB is a large integral membrane protein. In spite of postulated in vivo activities for PITPs, the function of RdgB in the photoreceptor cell remains unknown. Recently, vertebrate orthologues of the rdgB gene were identified in mice, bovines, and humans (Chang et al., 1997). Expression of the mouse rdgB cDNA in rdgB² null mutant flies resulted in the elimination of the retinal degeneration and complete restoration of the wild-type ERG light response (Chang et al., 1997). Thus, the Drosophila RdgB protein defines a new class of functionally equivalent transmembrane PITPs.In this work, we analyzed RdgB''s involvement in the Drosophila phototransduction cascade and the mechanism by which it prevents the onset of retinal degeneration. This represents the first in vivo analysis of the transmembrane PITP class, and we report several novel and unanticipated aspects of RdgB function. We demonstrate that the complete repertoire of RdgB functions essential for normal phototransduction reside in the PITP domain. Expression of this domain as a soluble polypeptide fully complements the rdgB² null allele. Yet, other PITPs that possess PI and/ or PC transfer activities in vitro cannot substitute for RdgB in the photoreceptor cell. Whereas the recessive rdgB² null mutation demonstrates an essential role for RdgB in proper termination of the ERG light response and dark recovery of the photoreceptor cell, one novel dominant rdgB mutation affects the maintenance of steady- state rhodopsin levels in photoreceptor cells. Another dominant rdgB mutation induces retinal degeneration and compromises the rapid regeneration of a wild-type ERG light-response amplitude subsequent to multiple or prolonged light exposure. Taken together, these data indicate an underlying complexity to the mechanism of RdgB function and its role in the photoreceptor cell that is not easily reconciled with a simple role in potentiating signal transduction via phosphoinositide-driven signaling pathways.     

Etiological structure and resistance to antibacterial drugs of causative agents of cross infection in Donetsk

Tests for hemocultures were performed in 51 patients with clinical diagnoses of sepsis treated in a reanimation unit. Microbial cultures were isolated from 30 patients (58.9 per cent). Staphylococci in pure cultures and associations were the causative agents of sepsis in 26 patients (86.4 per cent). The cultures of E. coli, Y. enterocolitica and Streptococcus faecalis were isolated from 2, 1 and 1 patients, respectively. Pus specimens from 111 patients with postinjection suppuration were tested and staphylococci in pure cultures and associations were detected in 90 patients (81.8 per cent). The cultures of P. vulgaris, Streptococcus pyogenes, E. coli, Str. faecalis, Enterobacter spp. and Pseudomonas aeruginosa were isolated from 10, 5, 3, 1, 1 and 1 patients, respectively. The results showed that Staphylococci played the leading role in development of the hospital infections. Treatment of such patients should be performed with an account of antibioticograms since many strains are resistant to various antibiotics.     

Anaerobic microflora of the female reproductive tract

The microflora of the female reproductive tract is very diverse and plays an important role in both normal and pathological states. The data on the mechanisms of colonization resistance which involve the vaginal microbios (the production of H2O2, organic acids, bacteriocin-like substances, competition for adhesion sites) are presented. The data on the role of individual antagonistically active substances of anaerobic bacteria in suppressing gonococci, fungi, microorganisms, associated with bacterial vaginosis, etc. are given. The leading role of anaerobic microorganisms in the appearance of microecological disturbances, including bacterial vaginosis, is emphasized. The role of the pathogenic properties of anaerobic bacteria for the development of different pathological processes, such as premature birth, postnatal and postoperative purulent septic diseases, inflammation of pelvic organs, cancer of the neck of uterus, is discussed.     

Perioperative management of focal liver diseases by ofloxacin]

Perioperative use of ofloxacin for prophylaxis was investigated in 20 patients with focal hepatic formations (hemangioma, adenocarcinoma, echinococcosis). First dose of ofloxacin (200 mg) was given intravenously 15 min before operation. After operation ofloxacin was used intravenously (400 mg daily) for 5 days. Pharmacokinetic investigation demonstrated that perioperative intravenous use of ofloxacin provided concentrations in blood and hepatic tissue satisfactory for potential microflore inhibition. Immunological monitoring demonstrated positive dynamics on 5-7 days after operation. dynamics depended on nosology of the focal hepatic formation. Ofloxacin use for prophylaxis in the operated patients with focal hepatic formations was efficient for profilaxy of postoperation infective complications.