Characterization of glycosaminoglycans from normal and fluoride treated rabbit iliac crest

Glycosaminoglycans from rabbit iliac crest was isolated and characterised. Glycosaminoglycans isolated from iliac crest reveals the presence of chondroitin sulphate A, chondroitin sulphate C and hyaluronic acid. However, glycosaminoglycans isolated from fluoride treated rabbit iliac crest shows the presence of dermatan sulphate (or chondroitin sulphate B) in addition to the above mentioned components. Significance of the appearance of dermatan sulphate in response to fluoride treatment is discussed.     

Proteolytic Cleavage of Type I Collagen Generates an Autoantigen in Autoimmune Uveitis

This study was initiated to induce experimental autoimmune anterior uveitis (EAAU) in Lewis rats by melanin-associated antigen (MAA; 22-kDa fragment of type I collagen α2 chain) derived from rat iris and ciliary body (CB), to localize MAA within the eye, and to investigate the possible mechanism of MAA generation in vivo. The EAAU model replicates idiopathic human anterior uveitis. Lewis rats sensitized to rat MAA developed anterior uveitis, and EAAU induced by rat MAA can be adoptively transferred to naive syngenic rats by MAA-primed T cells. Animals immunized with rat MAA developed cellular immunity to the antigen. MAA was detected only in the iris and CB of the eye. Iris and CB were the major source of matrix metalloproteinase-1 (MMP-1) in the naive eye, and ocular expression of MMP-1 was up-regulated, whereas expression of tissue inhibitor of metalloproteinase 1 decreased before the onset of EAAU. These results demonstrated that EAAU can be induced by autologous MAA. Uveitogenic antigen is present only in the iris and CB of the eye, and the imbalance between MMP-1 and tissue inhibitor of metalloproteinase 1 may play a role in the generation of MAA in vivo. Collectively, the evidence presented here suggests that MAA is an autoantigen in EAAU. These observations may extend to idiopathic human anterior uveitis and facilitate the development of antigen-specific therapy.     

Recognition and management of community-acquired acute kidney injury in low-resource settings in the ISN 0by25 trial: A multi-country feasibility study

BackgroundAcute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries.Methods and findingsPatients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27–62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily.ConclusionsThis multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care.

Etienne Macedo and colleagues report on a point-of-care testing program for acute kidney injury and disease in high-risk primary care patients.     

The recognition, distribution and ultrastructure of hydrozoan nerve elements

Silver stained Cordylophora were examined by light and electron microscopy, which provided a general picture of nerve cell forms and distribution for comparison with electron micrographs of osmium-fixed tissues from the same hydroid. Muscle, nerve and neurosensory components were studied in the nectophore of Nanomia (O. Siphonophora) and in the hydromedusae Sarsia and Euphysa by means of vital staining and optical and electron microscopy of epon sections; particular attention was given to relationships and interconnections between the cellular elements of the two marginal nerve rings. Mitochondrial size, numbers and types of vesicles and the occurrence of neurotubules and of parts of sensory cilia may provide useful ultrastructural clues for recognizing nerve elements, but serial sections are often needed to make identification conclusive. In Cordylophora and Nanomia, some neurites contain massed A vesicles (membrane-bounded dense granules) suggestive of neurosecretion (cf. reports on Hydra). However, a small type of A vesicle also occurs at synapses in Sarsia, indicating a probable role here in junctional transmission. Vesicles occur on both sides of some synapses (as previously reported for Cyanea) but on one side only in others, these being the first examples of polarized junctional ultrastructure in coelenterates.     

In infertile women,cells from <Emphasis Type="Italic">Chlamydia trachomatis</Emphasis> infected site release higher levels of interferon-gamma,interleukin-10 and tumor necrosis factor-alpha upon heat shock protein stimulation than fertile women

Background  

The magnitude of reproductive morbidity associated with sexually transmitted Chlamydia trachomatis infection is enormous. Association of antibodies to chlamydial heat shock proteins (cHSP) 60 and 10 with various disease sequelae such as infertility or ectopic pregnancy has been reported. Cell-mediated immunity is essential in resolution and in protection to Chlamydia as well as is involved in the immunopathogenesis of chlamydial diseases. To date only peripheral cell mediated immune responses have been evaluated for cHSP60. These studies suggest cHSPs as important factors involved in immunopathological condition associated with infection. Hence study of specific cytokine responses of mononuclear cells from the infectious site to cHSP60 and cHSP10 may elucidate their actual role in the cause of immunopathogenesis and the disease outcome.     

In vitro evaluation of the fermentation characteristics of the carbohydrate fractions of hulless barley and other cereals in the gastrointestinal tract of pigs

An in vitro model was used to study the fermentation characteristics of carbohydrate fractions of hulless barley (hB), in comparison to hulled barley (HB), hulled oat and oat groats (OG) in the pig intestine. For this purpose, 6 hulless barley cultivars (hB), varying in β-glucan content (36–99 g/kg DM), were compared to 3 HB cultivars, 2 oat groat samples (OG), 3 oat varieties and a reference sample of wheat. The residue of a pepsin–pancreatin hydrolysis was incubated in a buffered mineral solution inoculated with pig faeces. Gas production, proportional to the amount of fermented carbohydrates, was measured for 48 h and kinetics modelled. The fermented solution was subsequently analyzed for microbial production of short-chain fatty acids (SCFA) and ammonia. In vitro dry matter degradability varied according to ingredient (P<0.001). Higher values were observed for OG, ranging from 0.88 to 0.99 as compared to oat, hB and HB, for which degradability ranged from 0.63 to 0.73, 0.68 to 0.80 and 0.69 to 0.71, respectively. A “cereal type” effect (P<0.05) was observed on fermentation kinetics parameters. Total gas production was higher (P<0.05) with hB (224 ml/g DM incubated) than with HB and oat (188 and 55 ml/g DM incubated, respectively). No difference was observed between hB cultivars (P>0.05) for total gas production but differences (P<0.001) were found for lag time and the fractional rate of degradation. Hulless barley cultivar CDC Fibar (waxy starch) and CDC McGwire (normal starch) started to ferment sooner (lag time of 0.7 and 0.9 h, respectively) than SH99250 (high amylose starch; 1.7 h). The fractional rate of degradation was similar in both hB and OG (0.15/h on average), which was higher than that of HB (0.12/h). The production of SCFA was also higher (P<0.05) with hB (6.1 mmol/g DM incubated, on average) than with HB and oat (4.9 and 2.9 mmol/g DM incubated, respectively). Similar trends were found for SCFA production expressed per g fermented carbohydrates, with higher butyrate and lower acetate ratio. In contrast, oat fermentation generated higher (P<0.05) ammonia concentration (1.4 mmol/g DM incubated, on average) than hB (1.0 mmol/g DM incubated). In summary, hulless barleys, irrespective of cultivar type had higher in vitro fermentability and produced more SCFA and less ammonia than hulled barley and oat. Thus, hulless barleys have a better potential to be used in pig nutrition to manipulate the fermentation activity in the intestine of pigs.     

6,7,4′-trihydroxyisoflavan: A potent and selective inhibitor of 5-lipoxygenase in human and porcine peripheral blood leukocytes

The effect of 6,74′-trihydroxyisoflavan on human platelet 12-lipoxygenase and human and porcine PMNL 5-lipoxygenase activities has been studied. 6,7,4′-Trihydroxyisoflavan was found to inhibit 5-lipoxygenase more strongly than 12-lipoxygenase; its concentration for 50% inhibition (IC₅₀) was 1.6 μm for human and porcine 5-lipoxygenase adn 22 μM for human platelet 12-lipoxygenase. Inhibition of microsomal cyclooxygenase from ram seminal vesicles is exhibited at much higher concentrations of 6,7,4′-trihydroxyisoflavan (IC₅₀ = 200 μM).