Ranitidine-induced anaphylaxis: clinical features, cross-reactivity, and skin testing.

BACKGROUND: Histamine H2 receptor antagonists are commonly prescribed medications and are known to be well tolerated. However, 99 cases of ranitidine-induced anaphylaxis occurred in Korea from 2007 to 2014. OBJECTIVE: The purpose of this study was to determine the incidence, clinical features, and diagnostic methods for ranitidine-induced anaphylaxis. METHODS: Ranitidine-related pharmacovigilance data from 2007 to 2014 were reviewed. Adverse drug reactions with causal relationships were selected, and clinical manifestations, outcomes, and drug-related information were assessed. For further investigation, 8 years of pharmacovigilance data were collected at a single centre. Twenty-three patients participated in in vivo and in vitro studies. Skin tests, oral provocation tests, and laboratory tests were performed, including tests using other kinds of histamine H2 receptor antagonists. RESULTS: Over 7 years, 584 patients suffered adverse reactions to ranitidine. The most common manifestation was cutaneous symptoms. Among them, 99 patients (17.0%) experienced anaphylaxis. In a single-centre study, skin prick tests were positive in 91.7% of ranitidine-induced anaphylaxis patients (11/12); the optimal concentration was 20 mg/mL. Detection of ranitidine-specific immunoglobulin E failed. Cimetidine and proton pump inhibitors showed no cross-reactivity with ranitidine based on the skin prick test, oral provocation test, or clinical determination. Surprisingly, 82.6% of patients reintroduced ranitidine and re-experienced the same adverse reactions because ranitidine was not considered the culprit drug. CONCLUSIONS AND CLINICAL RELEVANCE: Although ranitidine is known as a safe drug, it can also cause diverse adverse reactions, including anaphylaxis. This study demonstrates the need to pay attention to adverse reactions to ranitidine and consider ranitidine as a cause of anaphylaxis.

Effects of cannabinoid receptor 1 (brain) on lipid accumulation by transcriptional control of CPT1A and CPT1B.

CB1 (also known as CNR1), a main receptor for cannabinoids acting at PPARs, can enhance fat deposition. Carnitine palmitoyltransferase-1 (CPT1), an enzyme responsible for the transport of long-chain fatty acids for ß-oxidation, is closely related to fat deposition. Whether CB1 can regulate intramuscular adipocytes lipid accumulation through regulation of CPT1 is unclear. Based on the investigation of tissue- and breed-specific CPT1A and CPT1B mRNA expression levels in Jinhua and Landrace pigs, we studied the effects of CB1 on lipid accumulation and CPT1B expression by treating porcine intramuscular adipocytes with CB1 antagonist Δ9-THC and antagonist SR141716. Results showed that muscle CPT1 mRNA was expressed at higher levels in the longissimus dorsi and subcutaneous fat. Liver CPT1A mRNA expression levels were higher in the pancreas, duodenum and liver. Compared with Landrace pigs, CPT1A and CPT1B in the longissimus dorsi of Jinhua pigs were significantly higher and positively correlated with intramuscular fat content. However, for subcutaneous fat, CPT1 levels were significantly lower and negatively correlated with body fat percentage. Δ9-THC significantly increased CB1 mRNA levels and lipid accumulation but decreased CPT1A and CPT1B mRNA levels. Conversely, SR141716 reduced CB1 mRNA levels but increased CPT1A and CPT1B mRNA levels, resulting in decreased lipid accumulation. The CPT1 antagonist etomoxir did not affect CB1 expression, suggesting that CB1 is likely upstream of CPT1A and CPT1B. Meanwhile, PPARA expression was greatly decreased when CPT1A and CPT1B were inhibited and enhanced when CPT1A and CPT1B were activated. Taken together, these data indicate that CB1 can affect intramuscular fat deposition by regulating both CPT1A and CPT1B mRNA expression, with the PPARA signal pathway likely playing a major role in this process.

Maximum thickness of subarachnoid blood is associated with mortality in patients with traumatic subarachnoid haemorrhage.

This study was designed to evaluate whether the maximum thickness of subarachnoid blood is an independent prognostic marker of mortality after traumatic subarachnoid haemorrhage. Multivariate analysis showed the maximum thickness of subarachnoid blood was an independent predictor of death versus survival 1 month after injury and was inversely associated with Glasgow Coma Scale (GCS) score. Receiver operating characteristic curve analysis showed that maximum thickness of subarachnoid blood > 6.7 mm immediately after non-surgical resuscitation predicted 1-month mortality with 83.9% sensitivity and 67.1% specificity; its predictive value was similar to that of the GCS score. Addition of maximum thickness of subarachnoid blood to the GCS score did not significantly improve predictive performance. Hence, the maximum thickness of subarachnoid blood is a new independent prognostic marker of mortality and might become an additional, valuable tool for risk stratification and decision making in the acute phase of traumatic subarachnoid haemorrhage.

Association of interleukin-11 with mortality in patients with spontaneous basal ganglia haemorrhage.

This study evaluated interleukin (IL)-11 as an independent prognostic marker of mortality following intracerebral haemorrhage (ICH). Plasma IL-11 levels in patients with ICH were significantly higher than in healthy controls. Multivariate analysis indicated that plasma IL-11 level was an independent predictor for mortality within 1 week of ICH onset and was positively associated with haematoma volume. Receiver operating characteristic curve analysis identified that a baseline plasma IL-11 level > 20.9 pg/ml predicted mortality within 1 week of ICH onset with 81.2% sensitivity and 74.1% specificity. The area under the curve for IL-11 level was significantly smaller than that for the Glasgow Coma Scale score, but similar to that for haematoma volume. IL-11 did not, however, significantly improve the predictive value of the Glasgow Coma Scale or haematoma volume. Thus, IL-11 may be considered as a new independent prognostic marker of mortality and an additional valuable tool for risk stratification and decision-making in the acute phase of ICH.

[1.4 kb 5' flanking region of class I patatin directs tuber-specific gus expression in potato (Solanum tuberosum L.)].

Binary vectors pPATIs (with partial signal sequence) and pPATI (without signal sequence) were constructed by fusing 1.4 kb 5' flanking regions of Class I patatin gene with GUS. Transient GUS expression was observed in in vitro tuber slices bombarded with pPATI. These constructs were then introduced into potato (cv. Desiree) via Agrobacterium tumefaciens transformation. Transgenic potato plants were confirmed by X-Gluc staining and PCR. Using in vitro tuberization system, GUS activities were assayed by fluorescence. It was shown that, in plants transformed with PATI-GUS, GUS specific activities were about 10-20 fold higher in tubers than in stems. Increased sucrose concentration could not induce PATI-GUS expression, but light enhanced PATI-GUS expression in cultured shoots.