Cardiac fibroblasts in pressure overload hypertrophy: the enemy within?

Cardiac fibroblasts have been long recognized as active participants in heart disease; however, their exact physiological and pathological roles remain elusive, mainly due to the lack of specific markers. In this issue of the JCI, Moore-Morris and colleagues used a fibroblast-specific collagen1a1-GFP reporter to demonstrate that fibroblast accumulation after aortic banding in murine hearts arises almost exclusively from proliferation of resident fibroblasts originating from both the epicardium and a previously unrecognized source, the endocardium. Further characterization of fibroblast origin and function in different types and stages of heart disease could lead to development of improved fibroblast-targeted cardiac therapies.     

Fetal and maternal plasma homocysteine levels during the second half of uncomplicated pregnancy

Objective: To measure fetal and maternal plasma homocysteine (Hcy) concentrations in uncomplicated pregnancies.

Methods: Paired maternal venous and fetal umbilical cord blood (n?=?81) samples were evaluated for plasma Hcy and vitamin B₁₂ levels, in addition to eight neonatal umbilical cord blood samples obtained immediately following delivery.

Results: Both fetal and maternal Hcy concentrations were positively correlated with advancing gestational age (ρ?=?0.44, p?<?0.0001; and ρ?=?0.27, p?<?0.05, respectively). Fetal plasma Hcy concentrations [2.2?µmol/l (IQR: 2.0–3.2)] were significantly lower than both neonatal umbilical vein [5.0?µmol/l (IQR: 4.4–6.5); p?<?0.001] and maternal plasma Hcy levels [4.4?μmo/l (IQR: 3.4–5.4); p?<?0.001]. In addition, Hcy values at term were higher in the umbilical vein compared with the umbilical artery [5.0?μmol/l (IQR: 3.4–5.4) versus 4.2?μmol/l (IQR: 3.7–5.5), respectively; p?=?0.016]. Significant correlation was noted and between fetal and maternal Hcy levels (ρ?=?0.50, p?<?0.0001), while fetal Hcy was negatively correlated with maternal B₁₂ concentrations (ρ?=??0.32, p?<?0.001).

Conclusions: Fetal Hcy levels were significantly lower than maternal and neonatal levels and correlated with gestational age across the second half of pregnancy.     

Investigating the effect of sotalol on the repolarization intervals in healthy young individuals

Background

The dissociation between a drug-induced increase of the QT interval prolongation and an increased risk for ventricular arrhythmias has been suggested by academic investigators and regulatory agencies. Yet, there are no alternative or complimentary electrocardiographic (ECG) techniques available for assessing the cardiotoxicity of novel compounds. In this study, we investigated a set of novel ECG parameters quantifying the morphology of the T-loop. In a group of healthy individuals exposed to sotalol, we compared their drug-induced changes to the drug-induced prolongations of the QTc, QTc apex and T-peak to T-end intervals.

Methods

We implemented a set of parameters describing the morphology of the T loop in its preferential plane. These parameters measure the time interval needed for the heart vector amplitude to change from its maximum value to a time when its amplitude has been reduced by 30%, 50%, and 70%. These measurements are called early repolarization duration (ERD) when they are located before the T-wave apex and late repolarization duration (LRD) when measured after the apex. They depend on both the speed of the repolarization process and the morphology of the T loop. Thirty-nine healthy individuals were exposed to sotalol in a crossover-design study. Sixteen ECGs were recorded per day during 3 days. The first day (day 0) was baseline; a single dose of sotalol (160 mg) was given during day 1, and a double dose was given during day 2 (320 mg). The plasma concentration of the drug was measured just before the ECG recordings.

Results

The values of all investigated parameters revealed a dose-dependent effect of sotalol (in average between parameters, ρ = 0.9, P < .001). Our investigations described profound and statistically significant changes in the morphology of the vectorial T loop for day 1 (peak effect of sotalol: ΔERD_50% = 23 ± 6 msec, P < .05; ΔLRD_50% = 8 ± 3 msec, P = .05) and day 2 (peak effect of sotalol: ΔERD_50% = 51 ± 14 msec, P < .05; ΔLRD_50% = 20 ± 12 msec, P = .05). When investigating the timing of peak drug concentration and peak effect of the drug on the various repolarization parameters, we found asynchrony between ERDs/LRDs (≥3.5 hours after dosing) and QTc/QTc apex profiles (<3.5 hours after dosing), suggesting that the time of maximum prolongation on the repolarization process was not synchronized with the time of maximum drug-induced heterogeneity of repolarization.

Conclusion

This study describes the sotalol-induced changes of the T-loop morphology in healthy individuals based on novel vectocardiographic parameters. These observations might help in improving the next generation of ECG markers for the evaluation of drug cardiotoxicity.     

Infantile peripheral neuropathy,deafness, and proximal tubulopathy associated with a novel mutation of the RRM2B gene

Mitochondrial DNA depletion syndromes are a group of autosomal recessive hereditary disorders characterized by reduction of the amount of mitochondrial DNA in the affected tissue (muscle, liver, brain, or kidneys). We report a case of an infant with myopathy, deafness, peripheral neuropathy, nephrocalcinosis, proximal renal tubulopathy, moderate lactic acidosis, and a novel mutation of the RRM2B gene.Mitochondrial DNA depletion syndromes are a group of autosomal recessive hereditary disorders characterized by reduction of the mitochondrial DNA amount in the affected tissue (1). Depletion of mitochondrial DNA can affect specific tissues or combination of organs and tissues including muscles, liver, brain, or kidneys (2,3).Different defects of nuclear genes may lead to different clinical manifestations, such as hepatocerebral syndrome, encephalopathy, or myopathy. One of the recently identified genes for mitochondrial DNA depletion syndromes is RRM2B, which encodes an isoform of a small subunit of ribonucleotide reductase. This enzyme plays an essential role in nucleotide synthesis, converting ribonucleotides to deoxyribonucleotides. Since 2008, 14 mutations of RRM2B gene have been reported (3,4). All the reported mutations are unique and there is no mutation that appears in more than one family (1-4).All reported patients had myopathy and primary lactic acidosis. More than a half of them died before the fourth month of age. The oldest patient with RRM2B mutation was a 42 years old woman with clinical findings suggestive of neurogastrointestinal encephalopathy (5). In this report, we review a case of an infant with muscular hypotonia, myopathy, peripheral neuropathy, deafness, nephrocalcinosis, proximal renal tubulopathy, moderate lactic acidosis, and a novel mutation of the RRM2B gene.     

Triglyceride lipase activity in bovine aorta.

The cell-free supernatant from homogenized bovine aorta hydrolyzed triglycerides, beta-naphthylesters of lauric and stearic acid and Tween 20, 40 and 60. The rate of hydrolysis decreases as the acyl chain length of the substrates increases. The activity against triglycerides of short-chain fatty acids and monoacylesters could be partially separated from that of glycerol-trioleate lipase by ammonium sulfate fractionation. The activity of glycerol-trioleate lipase remained unaffected by heating for 5 min at 60 degrees C or by addition of bile acids, whereas the activity causing hydrolysis of triglycerides with short-chain fatty acids and monoacylesters decreases up to 60% by analogous treatment.     

Psychiatric comorbidity in the treatment of patients with inflammatory bowel disease

Ulcerative colitis and Crohn’s disease,commonly known as inflammatory bowel disease(IBD),draw attention from specialists of various disorders,including gastroenterology,psychiatry,and radiology.The involvement of a cortical influence in the brain-gut axis as well as the interaction of the hypothalamic-pituitary-adrenal axis and the peripheral nervous system provide an initial explanation of the psychological symptoms associated with IBD.The involvement of structures the limbic system,such as the anterior cingulate cortex,the prefrontal cortex,and the amygdala,paves the way for the discovery of the mechanisms underlying depression depression,anxiety,alexithymia,personality traits,and other psychological impairments following the onset of IBD.Psychiatric therapy in IBD patients is almost as important as the gastroenterological approach and consists of pharmacological treatment and psychotherapy.Neither of the available psychiatric treatment methods is considered the golden standard because both methods have side effects,and psychotropic medication can provoke the worsening of IBD symptoms.Thus,both approaches must be applied with awareness of the possibility of side effects.We suggest that psychiatrists and gastroenterologists work together to reach a consensus on IBD therapy to ensure success and to reduce side effects and relapse to the lowest possible rates.     

Temperament and character modify risk of drug addiction and influence choice of drugs

Background: Drug addiction and alcoholism involve a complex etiopathogenesis with a variable degree of risk contributions from the host (person), environment, and addictive substances. In this work, temperament and character features of individuals addicted to opiates or alcohol are compared with normal controls to study personality factors in the overall risk for drug addiction. Methods: The study was done in a permissive environment, with easy access to alcohol and heroin, which facilitated analyses of personality factors in drug choice. Participants included 412 consecutive patients (312 opiate addicts, 100 alcohol addicts) treated at the Specialized Hospital for Chemical Dependency in Belgrade, Serbia, and a community sample of 346 controls. Results: Opiate addicts manifested antisocial temperament configuration (high Novelty Seeking, low Reward Dependence) coupled with high Self-transcendence (ie, susceptibility to fantasy and imagination). Alcohol addicts manifested sensitive temperament configuration (high Novelty Seeking coexisting with high Harm Avoidance). Immature personality was observed far more frequently in opiate addicts than in alcoholics or normals. Conclusions: Novelty Seeking appears to be a general risk factor for drug addiction. High Harm Avoidance appears to channel individuals with high Novelty Seeking towards alcoholism. Immature character traits and probable Personality Disorder increase the risk of illegal drugs. Based on equivalent research in nonpermissive environments, at least a portion of our opiate addicts could have developed alcoholism instead in environments with more limited access to opiates. Personality factors provide useful guidelines for preventive work with young individuals with personality risk factors for drug addiction. (Am J Addict 2012;21:462-467).     

Correlation between procalcitonin and intra-abdominal pressure and their role in prediction of the severity of acute pancreatitis

Background/aimsEarly assessment of disease severity and vigilant patient monitoring are key factors for adequate treatment of acute pancreatitis (AP). The aim of this study was to determine the correlation of procalcitonin (PCT) serum concentrations and intra-abdominal pressure (IAP) as prognostic markers in early stages of AP.MethodsThis prospective observational study included 51 patients, of which 29 had severe AP (SAP). Patients were evaluated with the Acute Physiology And Chronic Health Evaluation (APACHE II) score, C-reactive protein (CRP) and PCT serum concentrations and IAP at 24 h from admission. PCT was measured three times in the 1st week of disease and three times afterward, while IAP was measured daily. PCT and IAP values correlated with each other, and also compared with APACHE II score and CRP values.ResultsPCT, IAP, CRP values and APACHE II score at 24 h after hospital admission were significantly elevated in patients with SAP. There was significant correlation between PCT and IAP values measured at 24 h of admission, and between maximal PCT and IAP values. Sensitivity/specificity for predicting AP severity at 24 h after admission was 89%/69% for APACHE II score, 75%/86% for CRP, 86%/63% for PCT and 75%/77% for IAP.ConclusionsIncreased IAP was accompanied by increased PCT serum concentration in patients with AP. PCT and IAP can both be used as early markers of AP severity.     

Multiple co-infections of rodents with hantaviruses, Leptospira, and Babesia in Croatia

Hantaviruses, Leptospira spp., and Babesia spp. are rodent-borne pathogens present worldwide. We studied multiple co-infections of small rodents in Croatia with all three pathogens. Twenty-eight Apodemus flavicollis and 16 Myodes glareolus were tested for the presence of hantavirus RNA by real-time RT-PCR, Leptospira strains by renoculture method and Babesia DNA by PCR. Anti-hantavirus antibodies and anti-Leptospira antibodies were detected by serological methods. Very high infection rates with each pathogen were found in A. flavicollis: 20 of 28 rodents (71%) were infected with Dobrava virus, 13 rodents (46%) were infected with Leptospira, and 5 rodents (18%) were infected with Babesia. Multiple co-infections with all three pathogens were found in 3 of 28 (11%) A. flavicollis animals, suggesting that the same rodent host can be infected with several pathogens at the same time. Dual infections with both hantaviruses and Leptospira were found in 7 of 44 rodents (16%), with hantaviruses and Babesia in 2 rodents (5%), and double infection with both Leptospira and Babesia were found in 1 rodent (2%). Since hantaviruses, Leptospira, and Babesia have similar geographical distributions, it is to be expected that in other parts of the world multiple co-infections, representing a serious threat to public health, can be found.