Early Eosinophilic Antibody-mediated Rejection in a Renal Allograft Recipient.

Although the predominant component of acute allograft rejection is the T-cells, the milieu is not devoid of other inflammatory cells including plasma cells, eosinophils, and histiocytes. Apart from the CD8 T cell and CD4 T cell-FasL cytotoxicity, experimental models had proven a pivotal role of Th-2 cells in acute rejection, and these have been associated with marked tissue eosinophilia. Herein, we present a unique case of severe eosinophilic acute antibody-mediated rejection in a 22 years old deceased donor renal allograft recipient, within 4 days of transplantation without peripheral eosinophilia. The pathology was successfully dealt with the prevailing modalities of therapy, including steroids, plasmapheresis, intravenous immunoglobulin, and bortezomib. Concurrently, we have briefly reviewed the literature about the role of eosinophils in graft rejection and its prognostication.

Natural gum as mucoadhesive controlled release carriers: evaluation of cefpodoxime proxetil by D-optimal design technique.

The present study deals with the development of mucoadhesive controlled release tablets of Cefpodoxime Proxetil to increase the gastric residence time and thus prolong drug release, reduce dosing frequency and improve oral bioavailability. Tablets were prepared using sodium alginate and karaya gum, a natural polymer, with a synthetic polymer hydroxypropylmethylcellulose (K100LV) and Karaya gum with HPMC K100LV in various ratios to optimize the drug release profile using D-Optimal technique. Pre- and post-compression parameters of tablets prepared with various formulations (S1-S9, C1-C9) were evaluated. The FTIR and DSC studies revealed that no physiochemical interaction between excipients and drug. The formulation S7 showed prolonged drug release, and the mechanism of drug release from the optimized formulation was confirmed using the Korsmeyer-Peppas model to be non-Fickian release transport and n value was found 0.605 indicating both diffusion and erosion mechanism from these natural gums. The optimized formulation showed mucoadhesive strength >35 g. An in vivo study was performed on rabbits using an X-ray imaging technique. The radiological evidence suggests that the tablets adheres (more than 10 hours) to a rabbit's stomach. No significant changes were found in the physical appearance, drug content, mucoadhesive study and in vitro dissolution pattern after storage at 40 °C/75% relative humidity for 3 months.

Primary haemophagocytic syndrome in a young girl.

Haemophagocytic syndrome is a life-threatening systemic illness characterized by an uncontrolled inflammatory response. Patients present with fever, hepatosplenomegaly, jaundice and liver dysfunction, neurological manifestations and often pancytopenla. Bone marrow, lymph node, hepatic or splenic biopsy shows macrophages with Ingested blood cells or their precursors. Laboratory markers include elevated triglycerides and ferritin, low fibrinogen with normal or low erythrocyte sedimentation rate (ESR). Familial haemophagocytic lymphohistiocytosis (HLH) is an autosomal recessive disorder. Secondary haemophagocytic syndrome results from infections, malignancy and collagen vascular disorders. We describe a young girl with primary haemophagocytic syndrome.

Oxygen saturation profile in healthy preterm infants.

AIM: To establish a reference range for oxygen saturation (SpO(2)) in well preterm infants to guide home oxygen therapy using a pulse oximeter and Pulse Oximetry Data Analysis Software (PODS). METHODS: SpO(2) and heart-rate profiles of healthy preterm infants receiving mechanical ventilation for less than 6 h and supplemental oxygen for less than 48 h were monitored using a pulse oximeter. The stored data were downloaded from the monitor to a personal computer as individual files. Each infant's files of SpO(2) were subsequently displayed in graphic form, and a reference range was constructed using dedicated software, PODS. RESULTS: 43 infants were studied. The median value of all infants mean SpO(2) values was 95% (range 92-99%). The median duration of saturations less than 85% and between 85% and 90 % were 1% and 2% respectively. Using the study group median, 5th and 95th percentiles, a cumulative frequency curve of time against SpO(2) value was constructed (representing the reference range of SpO(2) profiles in healthy preterm infants). CONCLUSION: The SpO(2) reference range can be used as an easy and practical guide to compare SpO(2) profiles of infants on home oxygen therapy and guide their oxygen therapy.

Co-administration of monoisoamyl dimercaptosuccinic acid and Moringa oleifera seed powder protects arsenic-induced oxidative stress and metal distribution in mice.

Arsenic contamination of groundwater in the West Bengal basin in India is unfolding as one of the worst natural geo-environmental disasters to date. Chelation therapy with chelating agents is considered to be the best known treatment against arsenic poisoning; however, they are compromised with certain serious drawbacks/side-effects. Efficacy of combined administration of Moringa oleifera (M. oleifera) (English: Drumstick tree) seed powder, a herbal extract, with a thiol chelator monoisoamyl DMSA (MiADMSA) post-arsenic exposure in mice was studied. Mice were exposed to 100 ppm arsenic in drinking water for 6 months, followed by 10-days treatment with M. oleifera seed powder (500 mg/kg, orally through gastric gavage, once daily), MiADMSA (50 mg/kg, intraperitoneally, once daily) either individually or in combination. Arsenic exposure caused significant decrease in blood glutathione, delta-aminolevulinic acid dehydratase (ALAD), accompanied by increased production of reactive oxygen species in blood and soft tissues. Significant inhibition of superoxide dismutase, catalase, and glutathione peroxidase activities in tissues (liver in particular) along with significant increase in thiobarbituric acid reactive substances and metallothionein levels in arsenic intoxicated mice was also noted. Combined administration of MiADMSA with M. oleifera proved better than all other treatments in the recovery of most of the above parameters accompanied by more pronounced depletion of arsenic. The results suggest that concomitant administration of M. oleifera during chelation treatment with MiADMSA might be a better treatment option than monotherapy with the thiol chelator in chronic arsenic toxicity.

Comparative evaluation of some flavonoids and tocopherol acetate against the systemic toxicity induced by sulphur mustard.

OBJECTIVE: To evaluate the protective value of quercetin, gossypin, Hippophae rhamnoides (HR) flavone and tocopherol acetate against the systemic toxicity of percutaneously administered sulphur mustard (SM) in mice. MATERIALS AND METHODS: Quercetin, gossypin, HR flavone or tocopherol acetate (200 mg/kg, i.p.) were administered just before percutaneous administration of SM and protection against the SM lethality was evaluated. In another experiment quercetin, gossypin, HR flavone or tocopherol acetate were administered against 2 LD(50) SM. The animals were sacrificed seven days post SM administration and various biochemical parameters were estimated. RESULTS: The protection against the lethality of SM was very good with the flavonoids (quercetin = 4.7 folds; gossypin = 6.7 folds and HR flavone = 5.6 folds), compared to no protection with tocopherol acetate (0.7 fold). SM (2 LD(50)) showed decrease in reduced and oxidised glutathione (GSH and GSSG) levels, and an increase in malondialdehyde level (MDA). Oxidative stress enzymes like glutathione peroxidase, glutathione reductase and superoxide dismutase were significantly decreased. The total antioxidant status was also significantly decreased. Additionally, there was a significant increase in red blood corpuscles and hemoglobin content. All the flavonoids significantly protected the GSH, GSSG and MDA, and also the hematological variables. Tocopherol acetate failed to offer any protection in those parameters. Gossypin protected glutathione peroxidase, while HR flavone protected both glutathione reductase and glutathione peroxidase significantly. The decrease in body weight induced by SM and the histological lesions in liver and spleen were also significantly protected by the flavonoids but not by tocopherol acetate. CONCLUSION: The present study supports that SM induces oxidative stress and flavonoids are promising cytoprotectants against this toxic effect.

Evaluation of analogues of DRDE-07 as prophylactic agents against the lethality and toxicity of sulfur mustard administered through percutaneous route.

Sulfur mustard (SM), chemically bis (2-chloroethyl) sulfide is a bifunctional alkylating agent that causes serious blisters on contact with human skin. Although several antidotes have been reported for the systemic toxicity of SM in experimental animals none of them are approved so far and decontamination of SM immediately by physical or chemical means is recommended as the best protection. Two compounds amifostine [S-2(3-aminopropylamino) ethyl phosphorothioate] and DRDE-07 [S-2(2-aminoethylamino) ethyl phenyl sulfide] gave very good protection as an oral prophylactic agent against SM the in mouse model, but in the rat model the protection was only moderate. In the search for more effective and less toxic compounds, a number of analogues of DRDE-07 were synthesised and their protective efficacy was evaluated in mouse and rat models. The LD50 of S-aryl substitution was between 1 and 2 g kg(-1) and S-alkyl substitution was more than 2 g kg(-1). In the mouse model, DRDE-07, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 gave about 20 fold protection, and DRDE-23 and DRDE-38 gave less protection of 4.8 and 9.0 fold respectively, against percutaneously administered SM. In the rat model, DRDE-07, DRDE-09, DRDE-10 and DRDE-21 gave about two fold protection. Percutaneously administered SM (19.33 mg kg(-1)) significantly depleted the hepatic GSH content in mice. Pretreatment with DRDE-21 significantly elevated the levels. A 4.4 fold increase in % DNA fragmentation was observed 7 days after SM administration (19.33 mg kg(-1)) in mice. Pretreatment with DRDE-07, DRDE-09, DRDE-10, DRDE-21, DRDE-30 and DRDE-35 significantly protected the mice from SM induced DNA damage. The histopathological lesions in liver and spleen induced by percutaneously administered SM was reduced by pretreatment with DRDE-07, DRDE-09, DRDE-10 and DRDE-21. These analogues may prove as prototypes for the designing of more effective prophylactic drug for SM.