Influence of strain and age differences on the yields of porcine islet isolation: extremely high islet yields from SPF CMS miniature pigs

BACKGROUND: Porcine pancreas is a potential source of material for islet xenotransplantation. However, the difficulty in isolating islets, because of their fragility and the variability of isolation outcome in donor age and breed, represents a major obstacle to porcine islet xenotransplantation. In this study, we compared the islet isolation yield of specific pathogen-free (SPF) Chicago Medical School (CMS) miniature pigs with that of another miniature pig breed and market pigs from a local slaughterhouse. METHODS: Nine adult CMS miniature (ACM) pigs (>12 months), six young CMS miniature (YCM) pigs (6-7 months), four adult Prestige World Genetics (PWG) miniature (APM) pigs (>12 months), and 13 adult market (AM) pigs from a local slaughterhouse were used for islet isolation. RESULTS: The islet yield per gram of pancreas from ACM pigs (9589 +/- 2823 IEQ/g) was significantly higher than that from APM pigs (1752 +/- 874 IEQ/g, P < 0.05), AM pigs (1931 +/- 947 IEQ/g, P < 0.05), or YCM pigs (3460 +/- 1985 IEQ/g, P < 0.05). Isolated islets from ACM pigs were significantly larger than those from AM pigs or YCM pigs. The in vitro and in vivo function of isolated islets showed no difference among experimental groups. The pancreases of ACM pigs contained higher mean islet volume density percentages and larger size of islets than those of AM or APM pigs. CONCLUSIONS: We isolated extremely high yields of well-functioning islets from ACM pigs bred under SPF conditions. SPF CMS miniature pigs should be one of the best porcine islet donors for clinical porcine islet xenotransplantation.     

Benidipine has effects similar to losartan on the central blood pressure and arterial stiffness in mild to moderate essential hypertension

Background Central blood pressure (BP) is pathophysiologically more important than peripheral BP for the pathogenesis of cardiovascular disease.Arterial stiffness is also a good predictor of cardiovascular morbidity and mortality.The effects of benidipine,a unique dual L-/T-type calcium channel blocker,on central BP have not been reported.This study aimed to compare the effect of benidipine and losartan on the central BP and arterial stiffness in mild to moderate essential hypertensives.Methods This 24 weeks,multi-center,open label,randomized,active drug comparative,parallel group study was designed as a non-inferiority study.The eligible patients (n=200) were randomly assigned to receive benidipine (n=101)or losartan (n=99).Radial artery applanation tonometry and pulse wave analysis were used to measure the central BP,pulse wave velocity (PWV) and augmentation index (Alx).We also measured the metabolic and inflammatory markers.Results After 24 weeks,the central BP decreased significantly from baseline by (16.8+14.0/10.5+9.2) mmHg (1mmHg =0.133 kPa) (systolic/diastolic BP; P ＜0.001) in benidipine group and (18.9+14.7/12.1+10.2) mmHg (P ＜0.001)in losartan group respectively.Both benidipine and losartan groups significantly lowered peripheral BP (P ＜0.001) and Alx (P ＜0.05),but there were no significant differences between the two groups.The mean aortic,brachial and femoral PWV did not change in both groups after 24-week treatment.There were no significant changes of the blood metabolic and inflammatory biomarkers in each group.Conclusion Benidipine is as effective as losartan in lowering the central and peripheral BP,and improving arterial stiffness.     

Cytomegalovirus colitis induced segmental colonic hypoganglionosis in an immunocompetent patient: A case report

BACKGROUNDCytomegalovirus (CMV) colitis is usually seen in immunocompromised patients with risk factors such as human immunodeficiency virus infection, solid organ transplant, inflammatory bowel disease, or malignancy. Therefore, many clinicians usually do not consider the possibility of CMV colitis in immunocompetent patients. We reported a rare case of segmental colonic hypoganglionosis associated with CMV colitis in an immunocompetent patient. CASE SUMMARYA 48-year-old woman with no underlying disease was admitted to our hospital for severe abdominal pain and constipation. Computed tomography of the abdomen showed diffuse dilatation of the small intestine and the entire colon. Initial sigmoidoscopic findings and result of polymerase chain reaction (PCR) for CMV revealed the compatible findings of CMV colitis, the patient was treated with intravenous ganciclovir. After treatment, sigmoidoscopic findings and CMV PCR results improved. However the patient continued to suffered from constipation. Eight months after the initial admission, patient visited the emergency department with severe abdominal pain and imaging revealed aggravation of fecal impaction and bowel dilatation. We performed subtotal colectomy to control patient’s symptom. Histological examination of the resected specimen showed significantly reduced number of mature ganglion cells in the sigmoid colon compared to that in the proximal colon.CONCLUSIONOur case demonstrates that CMV colitis can develop even in patients with no other underlying disease, and that CMV colitis can be one of the causes for developing colonic hypoganglionosis.     

Association of MCP-1 and CCR2 polymorphisms with the risk of late acute rejection after renal transplantation in Korean patients

Among the factors modulating transplant rejection, chemokines and their respective receptors deserve special attention. Increased expression of monocyte chemoattractant protein-1 (MCP-1) and its corresponding receptor (chemokine receptor-2, CCR2) has been implicated in renal transplant rejection. To determine the impact of the MCP-1-2518G and CCR2-64I genotypes on renal allograft function, 167 Korean patients who underwent transplantation over a 25-year period were evaluated. Genomic DNA was genotyped using polymerase chain reaction followed by restriction fragment length polymorphism analysis. Fifty-five (32.9%) patients were homozygous for the MCP-1-2518G polymorphism. Nine (5.4%) patients were homozygous for the CCR2-64I polymorphism. None of the investigated polymorphism showed a significant shift in long-term allograft survival. However, a significant increase was noted for the risk of late acute rejection in recipients who were homozygous for the MCP-1-2518G polymorphism (OR, 2.600; 95% CI, 1.125-6.012; P = 0.022). There was also an association between the MCP-1-2518G/G genotype and the number of late acute rejection episodes (P = 0.024). Although there was no difference in the incidence of rejection among recipients stratified by the CCR2-V64I genotype, recipients with the CCR2-V64I GG genotype in combination with the MCP-1-2518G/G genotype had a significantly higher risk of acute or late acute rejection among the receptor-ligand combinations (P = 0.006, P = 0.008, respectively). The MCP-1 variant may be a marker for risk of late acute rejection in Korean patients.     

Formation of unconventional standing waves at graphene edges by valley mixing and pseudospin rotation

We investigate the roles of the pseudospin and the valley degeneracy in electron scattering at graphene edges. It is found that they are strongly correlated with charge density modulations of short-wavelength oscillations and slowly decaying beat patterns in the electronic density profile. Theoretical analyses using nearest-neighbor tight-binding methods and first-principles density-functional theory calculations agree well with our experimental data from scanning tunneling microscopy. The armchair edge shows almost perfect intervalley scattering with pseudospin invariance regardless of the presence of the hydrogen atom at the edge, whereas the zigzag edge only allows for intravalley scattering with the change in the pseudospin orientation. The effect of structural defects at the graphene edges is also discussed.     

Association of the plasma aldosterone concentration,left atrial deformation and ambulatory blood pressure in never-treated early hypertensive patients

Left atrial (LA) strain is known to exhibit an early progressive reduction in hypertensive patients with diastolic dysfunction. However, an association of the renin-angiotensin-*aldosterone system (RAAS) with LA deformation has not been found in these patients. We aimed to investigate the association of plasma aldosterone concentration (PAC) and 24-hour ambulatory blood pressure monitoring (ABPM) with LA and left ventricle (LV) deformation in never-treated early hypertensive patients. This cross-sectional study included 101 never-treated subjects who were registered in a working group at The Catholic University of Korea. The patients were divided into a hypertension group (n = 71), which was defined as having a systolic blood pressure (BP) ≥130 mm Hg and/or a diastolic BP ≥80 mm Hg based on ABPM, and a control group (n = 30). Enrolled patients underwent conventional and speckle tracking echocardiography, ABPM, and measurement of pulse wave velocity, PAC, and plasma renin activity. Compared with the control group, the hypertension group had significantly increased PAC, global longitudinal strain (GLS), atrial reservoir strain, atrial pump strain, and atrial systolic strain rate. LA pump strain was independently associated with nighttime systolic BP. PAC was correlated with GLS but not LA deformation in hypertensive patients without clinically apparent target organ damage. The raised LV pressure secondary to the nocturnal systemic pressure overload might be more strongly associated with LA deformation than with the RAAS.     

Is Multi-Drug Resistant Tuberculosis More Prevalent in HIV-Infected Patients in Korea?

The epidemiological synergy between human immunodeficiency virus (HIV) and tuberculosis (TB) is a major threat to public health. However, the association between HIV and multi-drug resistant tuberculosis (MDR-TB) is not clear. To explore the association between HIV and MDR-TB infection, a case-control study was performed in Korea. A total of 1606 culture-proven TB patients (45 HIV vs. 1561 non-HIV) from January 2006 to October 2014 were included in this analysis. MDR-TB rates were 11.1% and 8.2% in the HIV and non-HIV groups, respectively (p=0.42), thus indicating that MDR-TB was not significantly associated with HIV infection in Korea.     

Association between renin-angiotensin-aldosterone system-related genes and blood pressure in a Korean population

AIMS. Blood pressure control is influenced by various genetic and environmental factors, and genetic susceptibility is important in the development of essential hypertension. Because the renin-angiotensin-aldosterone system (RAAS) has a key role in vasoconstriction, vasodilation, and sodium and electrolyte balance, it is central in blood pressure control and so is an appropriate target in hypertension treatments. The present study assessed the association of RAAS-related genes with blood pressure and hypertension in a Korean population. Single nucleotide polymorphisms (SNPs, n = 114) in nine RAAS-related genes (AGT, REN, ACE, ACE2, AGTR1, CYP11B2, NR3C2, MAS1, and CMA1) were assessed for their correlation with blood pressure and hypertension using genotype data of 8842 individuals from the Korea Association Resource subject pool. MAJOR FINDINGS. Linear regression analysis revealed a statistically significant association with blood pressure of 10 SNPs in six genes (ACE, ACE2, CYP11B2, NR3C2, MAS1, and CMA1). An additional hypertension case-control study identified 10 SNPs in NR3C2 and ACE that were linked to hypertension. PRINCIPAL CONCLUSION. Three SNPs (rs11737660, rs6810951, and rs10519963) in NR3C2 correlate with both blood pressure and hypertension. Genetic polymorphisms in RAAS-related genes appear to be associated with hypertension in a Korean population.     

Characteristics and Management of Residual or Slowly Recurred Intracranial Aneurysms

Objective

Residual aneurysm from incomplete clipping or slowly recurrent aneurysm is associated with high risk of subarachnoid hemorrhage. We describe complete treatment of the lesions by surgical clipping or endovascular treatment.

Methods

We analyzed 11 patients of residual or recurrent aneurysms who had undergone surgical clipping from 1998 to 2009. Among them, 5 cases were initially clipped at our hospital. The others were referred from other hospitals after clipping. The radiologic and medical records were retrospectively analyzed.

Results

All patients presented with subarachnoid hemorrhage at first time, and the most frequent location of the ruptured residual or recurrent aneurysm was in the anterior communicating artery to posterior-superior direction. Distal anterior cerebral artery, posterior communicating artery, and middle cerebral artery was followed. Repositioning of clipping in eleven cases, and one endovascular treatment were performed. No residual aneurysm was found in postoperative angiography, and no complication was noted in related to the operations.

Conclusion

These results indicate the importance of postoperative or follow up angiography and that reoperation of residual or slowly recurrent aneurysm should be tried if such lesions being found. Precise evaluation and appropriate planning including endovascular treatment should be performed for complete obliteration of the residual or recurrent aneurysm.