Pharmacokinetics of cysteamine bitartrate following intraduodenal delivery

Cysteamine is approved for the treatment of cystinosis and is being evaluated for Huntington's disease and non‐alcoholic fatty liver disease. Little is known about the bioavailability and biodistribution of the drug. The aim was to determine plasma, cerebrospinal fluid (CSF), and tissue (liver, kidney, muscle) cysteamine levels following intraduodenal delivery of the drug in rats pretreated and naïve to cysteamine and to estimate the hepatic first‐pass effect on cysteamine. Healthy male rats (n = 66) underwent intraduodenal and portal (PV) or jugular (JVC) venous catheterization. Half were pretreated with cysteamine, and half were naïve. Following intraduodenal cysteamine (20 mg/kg), serial blood samples were collected from the PV or the JVC. Animals were sacrificed at specific time points, and CSF and tissue were collected. Cysteamine levels were determined in plasma, CSF, and tissue. The C_max was achieved in 5–10 min from PV and 5–22.5 min from JVC. The PV‐C_max (P = 0.08), PV‐AUC_0–t (P = 0.16), JVC‐C_max (P = 0.02) and JVC‐AUC_0–t (P = 0.03) were higher in naive than in pretreated animals. Plasma cysteamine levels returned to baseline in ≤120 min. The hepatic first‐pass effect was estimated at 40%. Peak tissue and CSF cysteamine levels occurred ≤22.5 min, but returned to baseline levels ≤180 min. There was no difference in CSF and tissue cysteamine levels between naïve and pretreated groups, although cysteamine was more rapidly cleared in the pretreated group. Cysteamine is rapidly absorbed from the small intestine, undergoes significant hepatic first‐pass metabolism, crosses the blood brain barrier, and is almost undetectable in plasma, CSF, and body tissues 2 h after ingestion. Sustained‐release cysteamine may provide prolonged tissue exposure.     

Gas geyser syndrome: An important preventable cause of disabling neurological events

To bring to light the greatly hazardous effects of the use of flue less gas geysers in the domestic setting. Over a period of two years (2008 to 2010) twenty six cases were documented as presenting with unexplained neurological events while bathing in an ill ventilated bathroom with a functional flue less gas geyser. The cases were mainly of three distinct prototypes namely seizure like episodes seen in 11 patients, carbon monoxide intoxication in 13 patients with near cardiac arrest in 4, and as a precipitating factor for epilepsy as seen in 2 cases. Out of the 13 cases presenting as carbon monoxide intoxication 4 had subtle cognitive defects and 2 developed early Parkinsonian features on follow up. To increase awareness regarding gas geyser induced epilepsy and associated carbon monoxide intoxication, both of which are entirely preventable conditions. We also wish to emphasize the importance of stringent and universal implementation of gas geyser usage and installation laws.     

Granulomatous and lymphocytic hypophysitis – are they immunologically distinct?

Hypophysitis includes three histopathologically distinct entities – granulomatous, lymphocytic and xanthomatous forms. Etiopathogenesis and the immunological differences among these is not well characterized. This study aims to explore the immunopathogenesis of granulomatous and lymphocytic forms of hypophysitis. Demographic, clinical, endocrine function and radiological features of 33 histologically confirmed cases of hypophysitis were reviewed. Immunophenotyping of inflammatory component was performed in 13/33 cases. Visual disturbances (46%), headache (36%), polyuria/polydipsia (6%), menstrual disturbance (6%) and galactorrhoea (6%) were the frequent presenting symptoms. Endocrine abnormalities were noted in 11/18 cases evaluated (61%). Hypothyroidism was the most common endocrine abnormality (33.33%) followed by hyperprolactinaemia (22%) and hypocortisolism (16.66%). On neuroimaging, sellar mass with variable contrast enhancement was observed. On histology, granulomatous hypophysitis (GH) was more common (84.84%) than lymphocytic hypophysitis (LH) (15.15%). In GH, the infiltrate had almost equal proportions of CD3+ T cells and CD68+ histiocytes. Cytotoxic T cells (CD8+) predominated [CD4:CD8 < 1]. CD20+ B cell component ranged from <5% to 50%. Fibrosis, necrosis and giant cells accompanied GH. LH in contrast, had CD4+ T‐helper cell predominance [CD4: CD8 > 1]. CD68+ histiocytes constituted <20% and CD20+ B cells, 5–40% of the infiltrates. In conclusion, GH revealed cytotoxic T cell and histiocyte rich infiltrate in contrast to CD4+ T‐cell predominance in LH suggesting that the two forms have distinct immunological mechanisms in evolution, an autoimmune process in LH and type IV hypersensitivity response in GH.     

PROP test: prediction of caries risk by genetic taste perception among the visually impaired children

The study sample consisted of 100 children with visual impairment aged 6–14 years. 6‐n‐propylthiouracil (PROP) sensitivity test was carried out. The Caries experience was recorded, estimation of Streptococcus mutans done and their taste likes and dislikes assessed through a food preference questionnaire. The Caries experience and S. mutans levels were highest in the non‐tasters, comparatively low in medium tasters and the least in the supertasters. Dietary preferences indicated tasters were sweet dislikers and non‐tasters, sweet likers. PROP test can be a useful tool in determining genetic taste sensitivity levels amongst the visually impaired children and thus used as a screening tool in those children who are at a high risk of developing dental caries.     

Comparative analysis of different methods used for molecular characterization of Burkholderia cepacia complex isolated from noncystic fibrosis conditions

PurposeBurkholderia is a Gram-negative opportunistic bacterium capable of causing severe nosocomial infections. The aim of this study was to characterize Burkholderia cepacia complex and to compare different molecular methods used in its characterization.MethodsIn this study, 45 isolates of Burkholderia cepacia complex (Bcc) isolated from clinical cases were subjected to RAPD (Random amplified polymorphic DNA), recA-RFLP (Restriction fragment length polymorphism), 16SrDNA-RFLP, whole-cell protein analysis, recA DNA sequencing and biofilm assay.ResultsOf the 45 isolates tested, 97.7% were sensitive to ceftazidime, 82.2% were sensitive to Cotrimoxazole, 73.3% were sensitive to meropenem, 55.5% were sensitive to minocycline and 42.2% were sensitive to levofloxacin. Majority of the isolates harbored all the tested virulence genes except bpeA and cblA. The RAPD generated 11 groups (R1-R11), recA-RFLP 10 groups (A1-A10), 16SrRNA-RFLP 5 groups (S1–S5) and SDS-PAGE (Sodium Dodecyl Sulphate-Polyacrylamide gel electrophoresis) whole cell protein analysis revealed 12 groups (C1–C12). recA sequencing revealed that most of the isolates belonging to the genomovar III Burkholderia cenocepacia. Though all the methods are found to be efficient in differentiating Burkholderia spp., recA-RFLP was highly discriminatory at 96% similarity value. The study also identified a new strain Burkholderia pseudomultivorans for the first time in the country. Further, recA sequencing could identify the strains to species level. Majority of the multidrug-resistant strains also showed moderate to strong biofilm-forming ability, which further contributes to the virulence characteristics of the pathogens.ConclusionsThe study highlights the importance of combination of molecular methods to characterize Burkholderia cepacia complex. Molecular typing of these human pathogens yields important information for the clinicians in order to initiate the most appropriate therapy in the case of severe infections and to implement preventive measures for the effective control of transmission of Burkholderia spp.     

Thrombocytopenia in children with malaria–A study from coastal Karnataka,India

ObjectiveTo study the occurrence and severity of thrombocytopenia in children with malaria.MethodsIt was a retrospective study, done at Fr Muller Medical College Hospital Mangalore, in Karnataka, India. Data regarding all positive cases of malaria < 15 years admitted in the hospital between January 2010 to June 2011 were obtained. Patients were further assessed for thrombocytopenia and its severity. Data were analysed by Chi square test using SPSS version 13.0.ResultsA total of 159 cases were included in the study with a mean age of presentation of 9 years. Plasmodium vivax was identified in 106 (66%) patients while Plasmodium falciparum in 26 (16%) and mixed infection in 27 (18%) patients. Thrombocytopenia was observed in 113 (71%) cases, of which 35 (31%) cases had mild, 49 (43%) cases moderate and 29 (26%) cases had severe thrombocytopenia. Thrombocytopenia was equally found in vivax and falciparum infection with no significant difference in severity between vivax and falciparum species.ConclusionsThrombocytopenia is frequently seen in malaria and it is not dependent on type of malaria. In any acute febrile illness, thrombocytopenia should alert one to the possibility of malaria.