Transrectal ultrasonography and plasma progestin profiles identifies feto-placental compromise in mares with experimentally induced placentitis

Transrectal ultrasonography of the caudal uterus and a progestin profile were evaluated for accuracy in identifying mares with feto-placental compromise in a model of placentitis. Twenty-two pregnant ponies were divided into four groups: (1) control mares (n=5); (2) instrumented controls (n=2); (3) instrumented inoculated mares (n=11); (4) inoculated mares (n=4). Mares in Groups 3 and 4 were inoculated with Streptococcus equi subsp. zooepidemicus. Maternal plasma progestins, vulvar discharge, mammary gland development, combined thickness of the uterus and placenta (CTUP) and placental separation were evaluated weekly before instrumentation, inoculation or Day 320 (Groups 1 and 2) and, thereafter, either daily (first three measurements) or several times weekly (last two measurements). Plasma progestin profiles were plotted to identify pattern characteristics. An abbreviated profile was created, consisting of four progestin samples collected at 48-h intervals, with Sample 1 collected the day before inoculation or on Day 285 in controls. Profiles were considered abnormal if Samples 2, 3, or 4 increased or decreased by more than 50% of Sample 1. A CTUP>1.0 cm or placental separation were considered abnormal. Placentitis was confirmed by histology of fetal membranes. Control mares had normal progestin profiles, transrectal ultrasonographic and clinical examinations. Control foals were born after Day 329; six were viable and one died after dystocia. All inoculated mares developed placentitis and foaled before Day 314. Thirteen of 15 foals were not viable. All inoculated mares had abnormal progestin profiles and 13 of the 15 were identified by the abbreviated progestin profile. Transrectal CTUP was affected by gestational age and increased after inoculation (P<0.05). Nine of 15 inoculated mares had a CTUP>1.0 cm by 5-day post-inoculation. By performing both tests, 20 of 22 mares were correctly identified with respect to pregnancy outcome. However, three inoculated mares exhibited minimal clinical signs and likely would not be examined in a clinical setting. These tests were diagnostic for identifying feto-placental compromise in the mare.     

Neuroprotective efficacy of 4-Hydroxyisoleucine in experimentally induced intracerebral hemorrhage

Intracerebral hemorrhage (ICH) is a severe form of brain injury, which is a major cause of mortality in humans. Hydrocephalus and cerebral hematoma lead to severe neurological deficits. A single autologous blood (ALB) injection in rats' brains induces hemorrhage and other conditions that regularly interfere with the standard treatment of several cellular and molecular pathways. Several studies have found that IGF-1/GLP-1 decreases the production of inflammatory markers in peripheral tissues, while some have found that they also have pro-inflammatory functions. Since these receptors are down-regulated in hemorrhagic situations, we looked into the potential neuroprotective effect of 4-hydroxyisoleucine (4-HI); 50 mg/kg and 100 mg/kg, an active compound Trigonellafoenum-graecum, on post-hemorrhagic deficits in rats. Long-term oral administration of 4-HI for 35 days has improved behavioral and neurochemical deficits and severe pathological changes and improved cellular and molecular markers, apoptotic markers in the ALB-induced ICH experimental model.Furthermore, the findings revealed that 4-HI also improved the levels of other neurotransmitters (Ach, DOPA, GABA, glutamate); inflammatory cytokines (TNF-alpha, IL-1β, IL-17), and oxidative stress markers (MDA, nitrite, LDH, AchE, SOD, CAT, GPx, GSH) in the brain when evaluated after Day 35. There is no proven treatment available for the prevention of post-brain hemorrhage and neurochemical malfunction; available therapy is only for symptomatic relief of the patient. Thus, 4-HI could be a potential clinical approach for treating post-brain haemorrhage and neurochemical changes caused by neurological damage. Furthermore, 4-HI may be linked to other standard therapeutic therapies utilized in ICH as a potential pharmacological intervention.     

The combination of trimethoprim and sulfamethoxazole in the treatment of urinary tract infection

In a series of 52 patients the combination of trimethoprim and sulfamethoxazole was used for the treatment of urinary tract infection and the results are analyzed with respect to the clinical diagnosis and bacterial etiology. There was complete agreement between in vitro sensitivity and clinical response except in the case of one strain of Streptococcus fecalis. The combination of drugs was effective against some bacterial strains which were resistant to the commonly used antimicrobial agents.     

A survey on head lice infestation in Korea (2001) and the therapeutic efficacy of oral trimethoprim/sulfamethoxazole adding to lindane shampoo

Total of 7,495 children including 3,908 boys and 3,587 girls from a kindergarten and 15 primary schools were examined for head lice infestation (HLI). The overall prevalence of HLI in this study was found to be 5.8%. Head lice were much more commonly detected in girls than in boys with prevalence of 11.2% and 0.9%, respectively. Sixty-nine children with HLI were treated with 1% lindane shampoo alone (group 1), and 45 children with HLI were treated with 1% lindane shampoo and oral trimethoprim/sulfamethoxazole (group 2), and follow-up visits were conducted 2 and 4 weeks later. The children who still had HLI 2 weeks after the primary treatment were treated again. At the 2-week follow-up visit, the treatment success rates of groups 1 and 2 were 76.8% and 86.7%, respectively, and at the 4-week follow-up visit, the rates were 91.3% and 97.8%, respectively. No statistically significant synergistic effect was observed for the combination of a 1% lindane shampoo and oral trimethoprim/sulfamethoxazole.     

A new type of conjugative transposon encodes resistance to sulfamethoxazole, trimethoprim, and streptomycin in Vibrio cholerae O139.

Vibrio cholerae O139 is the first non-O1 serogroup of V. cholerae to give rise to epidemic cholera. Apparently, this new serogroup arose from an El Tor O1 strain of V cholerae, but V. cholerae O139 is distinguishable from V. cholerae El Tor O1 by virtue of its novel antigenic structure and also its characteristic pattern of resistances to the antibiotics sulfamethoxazole, trimethoprim, streptomycin, and furazolidone. We found that the first three of these antibiotic resistances are carried on an approximately 62-kb self-transmissible, chromosomally integrating genetic element which we have termed the SXT element. This novel conjugative transposon-like element could be conjugally transferred from V. cholerae O139 to V cholerae O1 and Escherichia coli strains, where it integrated into the recipient chromosomes in a site-specific manner independent of recA. To study the potential virulence properties of the SXT element as well as to improve upon the live attenuated O139 vaccine strain Bengal-2, a large internal deletion in the SXT element was crossed on to the Bengal-2 chromosome. The resulting strain, Bengal-2.SXT(s), is sensitive to sulfamethoxazole and trimethoprim and colonizes the intestines of suckling mice as well as wild-type strains do, suggesting that the SXT element does not encode a colonization factor. Derivatives of Bengal-2.SXT(s) are predicted to be safe, antibiotic-sensitive, live attenuated vaccines for cholera due to the O139 serogroup.     

Degradation of diclofenac,trimethoprim, carbamazepine,and sulfamethoxazole by laccase from Trametes versicolor: Transformation products and toxicity of treated effluent

Abstract

The degradation of diclofenac (DCF), trimethoprim (TMP), carbamazepine (CBZ), and sulfamethoxazole (SMX) by laccase from Trametes versicolor was investigated. Experiments were conducted using the pharmaceuticals individually, or as a mixture at different initial concentrations (1.25 and 5?mg/L each). The initial enzymatic activity of all the treated samples was around 430–460?U_(DMP)/L. The removal of the four selected pharmaceuticals tested individually was more effective than when tested in mixtures under the same conditions. For example, 5?mg DCF/L was completely removed to below its detection limit (1?µg/L) within 8?h in the individual experiment vs. after 24?h when dosed as a mixture with the other pharmaceuticals. A similar trend was visible with other three pharmaceuticals, with 95 vs. 39%, 82 vs. 34% and 56 vs. 49% removal after 48?h with 5?mg/L of TMP, CBZ, and SMX tested individually or as mixtures, respectively. In addition, at the lower initial concentration (1.25?mg/L each), the removal efficiency of TMP, CBZ, and SMX in mixtures was lower than that obtained at the higher initial concentrations (5?mg/L each) during both the individual and combined treatments. Four enzymatic transformation products (TPs) were identified during the individual treatments of DCF and CBZ by T. versicolor. For TMP and SMX, no major TPs were observed under the experimental conditions used. The toxicity of the solution before and after enzymatic treatment of each pharmaceutical was also assessed and all treated effluent samples were verified to be non-toxic.     

Treatment and mechanism of fecal microbiota transplantation in mice with experimentally induced ulcerative colitis

Restoring intestinal microbiota dysbiosis with fecal microbiota transplantation is considered as a promising treatment for ulcerative colitis. However, the mechanisms underlying its relieving effects remain unclear. Ulcerative colitis pathogenesis is associated with the involvement of immune cells and inflammatory cytokines. Here, we aimed to investigate the effect of fecal microbiota transplantation on T cell cytokines in a dextran sulfate sodium-induced ulcerative colitis mouse model. Five-aminosalicylic acid (5-ASA) was used as the positive control. Male C57BL/6 mice were randomly assigned to control, model (UC), UC + FMT, and UC + 5-ASA groups. Each group consisted of five mice. The establishment of the mouse model was verified by fecal occult-blood screening and hematoxylin–eosin staining. Results showed that fecal microbiota transplantation reduced colonic inflammation, significantly decreased T helper (Th)1 and Th17 cells, interferon-gamma, interleukin-2 and interleukin-17, as well as significantly increased Th2 and regulatory T (Treg) cells, interleukin-4, interleukin-10, and transforming growth factor-beta, and improved routine blood count. Furthermore, 16S rRNA gene-sequencing analysis showed a significant increase in the relative abundance of genus Akkermansia and a significant decrease in the relative abundance of genus Helicobacter in the ulcerative colitis group. Fecal microbiota transplantation restored the profile of the intestinal microbiota to that of the control group. These findings demonstrated the capability of fecal microbiota transplantation in controlling experimentally induced ulcerative colitis by improving Th1/Th2 and Th17/Treg imbalance through the regulation of intestinal microbiota.     

Determination of trimethoprim and sulfamethoxazole (co-trimoxazole) in body fluids of man by means of high-performance liquid chromatography

A high-performance liquid chromatographic method for the determination of trimethoprim, sulfamethoxazole and its metabolite and a series of structurally related sulfonamides is described. The half-life time of elimination of sulfamethoxazole and its metabolite N₄-acetylsulfamethoxazole is 9 h for both compounds. The renal excretion rate of sulfamethoxazole depends strongly on the urinary pH. The renal excretion rate of the metabolite N₄-acetylsulfamethoxazole is not dependent on the urinary pH.     

Antitumour efficacy of lymphokine-activated killer cells loaded with ricin against experimentally induced lung metastases

Summary Adoptive transfer of tumour-specific T lymphocytes loaded with ricin into tumour-bearing mice exerts a transient therapeutic effect against locally induced tumours [Cerundolo et al. (1987) Br J Cancer 55: 413]. As transferred cells preferentially locate in the lung, we studied the therapeutic effect of ricin-loaded, lymphokine-activated killer (LAK) cells on lung metastases induced by M4 or B16-F1 (F1) tumour cell injection. In vitro studies demonstrated that ricin-treated LAK cells were about 100-fold more efficient than untreated LAK cells in inhibiting growth of the ricin-sensitive M4 tumour cell line. This effect was most likely due to the released ricin, as treated and untreated LAK cells inhibited the relatively toxin-resistant F1 cell line to the same extent. Ricin treatment did not alter the tissue distribution of intravenously (i.v.) injected LAK cells, which selectively localized in the lung early after inoculation, whether or not metastases were present. Adoptive transfer experiments showed that ricintreated LAK cells were significantly more efficient than untreated LAK cells in inhibiting M4- but not F1-induced lung metastases. These results indicate that LAK cells are able to deliver a therapeutic concentration of antineoplastic compounds directly to the lung.Research activities were partially developed in relation to a contract with the National Program of Pharmacological Research (Rif. 078606), by the Italian Consortium for Antitumoral Vectors (C.I.V.A) for the Italia Ministry of University and Scientific and Technological Research     

The relative efficacy of aminoguanidine and pentoxifylline in modulating endotoxin-induced cardiac stress

This study investigates the effect of aminoguanidine (AG), a selective inducible nitric oxide synthase (iNOS) inhibitor, and pentoxifylline (PTX), a tumour necrosis factor–alpha (TNF‐α) inhibitor, on lipopolysaccharide (LPS)‐induced cardiac stress. Rats were divided into four groups: group I served as a control, group II (LPS) received a single intraperitoneal injection of LPS (10 mg·kg^–1), group III (LPS+AG) and group IV (LPS+PTX) were injected with either AG (100 mg·kg^–1) or PTX (150 mg·kg^–1) intraperitoneally 10 days prior to LPS administration. Normalization of cardiac levels of nitrite/nitrate (NO_X), malondialdehyde (MDA), glutathione (GSH), heme oxygenase‐1 (HO‐1), glutathione peroxidase (GPx) and Na⁺, K⁺‐ATPase activities was evident in the AG group. Both AG and PTX decreased the elevated serum TNF‐α levels, the activities of lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac myeloperoxidase (MPO). The levels of adenosine triphosphate (ATP), adenosine diphosphate (ADP) and phosphocreatine (PCr) were enhanced following AG and PTX pretreatments. Calcium (Ca²⁺) levels were altered, and the histopathological observations supported the described results. Conclusively, the study highlights the cardioprotective potential of AG and PTX with superior results from AG. These findings reveal the relative contribution of nitric oxide and TNF‐α to oxidative stress and energy failure during endotoxemia. Copyright © 2011 John Wiley & Sons, Ltd.     

High-performance liquid chromatography method for the simultaneous determination of sulfamethoxazole and trimethoprim in bovine milk using an on-line clean-up column

A bidimensional HPLC method for the simultaneous determination of sulfamethoxazole (SMX) and trimethoprim (TMP) in bovine milk has been developed and validated. After centrifugation, aliquots (150 microl) of milk samples were directly injected to a column-switching HPLC system. At the first step a RAM octyl-BSA column was employed to automatically remove proteins that otherwise would interfere with milk analysis. The mobile phase 0.01 M phosphate buffer pH 6.0:acetonitrile (95:5, v/v) was used in the first 5 min for the elution of milk proteins and then 0.01 M phosphate buffer pH 6.0:acetonitrile (83:17, v/v) for transfer SMX and TMP to the analytical column. The separation of SMX and TMP from one another and from other remaining milk components was performed on an octyl column using the mobile phase 0.01 M phosphate buffer pH 5.0:acetonitrile (82:18, v/v), which were detected by UV at 265 nm. The calibration graphs were linear in the concentration ranges of 25-800 ng/ml and 50-400 ng/ml for SMX and TMP, respectively. The intra- and inter-assay coefficients of variation were less than 15% for both drugs. The validated method was applied to the analysis of milk samples of twelve (two groups of six) cows after administration (intramuscular or subcutaneous) of a single recommended therapeutic dose of the SMX-TMP combination.     

Antilipoperoxidative and membrane stabilizing effect of diosgenin,in experimentally induced myocardial infarction

Molecular and Cellular Biochemistry - Altered membrane integrity has been suggested as a major factor in the development of cellular injury during myocardial necrosis. The present study was...     

Lesions of experimentally induced Tyzzer's disease in Syrian hamsters, guineapigs, mice and rats

The relative susceptibilities of C57BL/6NCR and BALB/cANNCR mice, F344/NCR rats, 2/NCR guineapigs and CR:RGH Syrian hamsters to Bacillus piliformis infection were determined by orally inoculating 20 weanling females from each species with suspensions of B. piliformis spores. Animals from each group were sequentially necropsied over 2 week periods to document the lesions produced. No significant gross or microscopic lesions were observed in the BALB mice or the Fischer rats. Gross and microscopic lesions were observed in the livers and intestines of many guineapigs and hamsters killed 3-14 days after inoculation. A large lesion was observed in the left cardiac ventricle of one C57BL mouse 10 days after inoculation. Warthin-Starry silver-stained tissue sections revealed clusters of B. piliformis within the cytoplasm of intestinal epithelial cells, smooth muscle cells, hepatocytes and myocytes bordering foci of necrosis in the intestines, liver and heart.     

Therapeutic efficacy of pentoxifylline on proteinuria and renal progression: an update

Blood pressure control with renin-angiotensin system (RAS) blockade has remained the gold standard for treating patients with proteinuric chronic kidney disease (CKD) up to date. Nevertheless, RAS blockade slows but does not halt the progression of kidney disease, thus highlighting the need to search for additional therapeutic approaches. The nonselective phosphodiesterase (PDE) inhibitor pentoxifylline (PTX) is an old drug that exhibits prominent anti-inflammatory, anti-proliferative and anti-fibrotic activities both in vitro and in vivo. Studies in human subjects have shown that PTX monotherapy decreases urinary protein excretion, and add-on therapy of PTX to background RAS blockade additively reduces proteinuria in patients with CKD of various etiology. More recent studies find that PTX combined with RAS blockade delays the decline of glomerular filtration rate in diabetic patients with mild to moderate CKD, and reduces the risk of end-stage renal disease in diabetic and non-diabetic patients in late stage of CKD with high proteinuria levels. In this review, we update the clinical trial results of PTX as monotherapy, or in conjunction or in comparison with RAS blockade on patients with proteinuria and CKD, and propose a mechanistic scheme explaining the renoprotective activities of this drug.     

Simultaneous determination of sulfamethoxazole and trimethoprim in biological fluids for high-throughput analysis: comparison of HPLC with ultraviolet and tandem mass spectrometric detection

The comparison of two methods based on online solid phase extraction-liquid chromatography with UV (SPE-LC-UV) or mass spectrometry detection (SPE-LC-MS/MS) for the simultaneous quantification of sulfamethoxazole (SMZ) and trimethoprim (TMP) is presented. The methods were validated and proved to be accurate. The analysis of standard samples for SMZ at concentrations of 0.5, 1.5, 25 and 50microg/mL demonstrated a relative standard deviation of less than 6% for both methods (n=18), while TMP samples at concentrations of 0.05, 0.15, 1.5 and 5.0microg/mL were analyzed with R.S.D. of less than 4% (n=18). The method with mass spectrometric detection was approximately six times more sensitive than the method with ultraviolet detection. The total run time for the SPE-LC-MS/MS was 2.5min per sample as opposed to 18.0min for the SPE-LC-UV method. The method with MS detection in comparison with UV detection proved to be more rugged and was successfully applied to pharmacokinetics studies.