Kidney transplantation for end‐stage renal disease secondary to familial Mediterranean fever

Although kidney transplantation (KT) is widely used for treating renal amyloidosis secondary to familial Mediterranean fever (FMF), data concerning transplant outcome are limited and inconsistent. The aim of this study was to determine the long‐term outcome of KT in patients with amyloidosis secondary to FMF. Kidney transplantation outcome in 24 patients with FMF was compared to that in 72 controls matched for age, gender of recipient, and type of the donor that underwent KT due to end‐stage renal disease (ESRD) not caused by FMF. Mean follow‐up time was 80.3 ± 55.1 months in the FMF group, vs. 86.5 ± 47.6 months in the control group. Death‐censored graft survival at five and 10 yr in the FMF group was 95.8% and 78.4%, respectively, and was comparable to that in the control group. In the FMF group, five‐ and 10‐yr patient survival (87.5 and 65.6%) was shorter than in the control group, but the difference was not statistically significant. The findings show that long‐term outcome of KT in the patients with amyloidosis secondary to FMF was comparable to that in patients with ESRD not caused by FMF. Recurrence of amyloidosis in the allograft, gastrointestinal intolerance, and fatal infections remain as major complications during the post‐transplant period.     

Immunohistochemical changes related to ageing in the mouse hippocampus and subventricular zone

We investigated mainly immunohistochemical changes of nestin (a marker of neuroepithelial stem cells) and Ki-67 (a marker of proliferating cells) proteins related to ageing in the mouse hippocampus and subventricular zone (SVZ) using young adult (8 weeks old) and middle-aged (40 weeks old) mice. In the present study, no significant changes in neurons and astrocytes of the hippocampal CA1 sector were found in a middle-aged male ICR mice without severe senile weakness, as compared with young adult animals. In contrast, a significant change in the number of microglia was found in the hippocampal CA1 sector of the middle-aged mice. Furthermore, no significant changes in the number of nestin- and Ki-67-positive cells were observed in the hippocampal CA1 sector of the middle-aged mice. On the other hand, decreases in the number of nestin- and Ki-67-immunopositive cells were observed in the SVZ of the middle-aged mice. Furthermore, a migration of nestin- and Ki-67-immunoreactive cells in the corpus callosum was not observed in the SVZ of the middle-aged mice. In the dentate gyrus, significant decreases in the number of Ki-67-immunopositive cells were observed in the middle-aged mice. Our study also showed that nestin immunoreactivity was observed in both Ki-67-postive cells and astrocytes in the SVZ of young adult mice. These findings emphasize the need to recognize ageing as important factors in studies of microglia, which may help to clarify the role of glial cell structure and function during ageing processes. Furthermore, the present findings suggest that ageing processes may decrease neurogenesis in the corpus callosum, SVZ and dentate gyrus. Thus our present findings provide valuable information for the neurogenesis during ageing processes.     

Evaluating a single dental anxiety question in Finnish adults

OBJECTIVE: To evaluate the psychometric properties (criterion validity, construct validity, sensitivity, and specificity) of a single-item question screening for dental anxiety in a Finnish adult population. MATERIAL AND METHODS: A total of 823 subjects, ranging in age from 18 to 87 years, answered a questionnaire comprising sections assessing the respondents' demographic profile and dental attendance patterns. A single dental anxiety question and the Modified Dental Anxiety Scale (MDAS) were included. The final response rate was 85%. RESULTS: Eight percent of the sample was highly dentally anxious using the MDAS cut-off point of 19 or above. Twelve percent of the respondents rated themselves as "very scared" on the single-item question. The percentage agreement between the single-item question and the MDAS was 93; the Kappa coefficient was 0.63. Specificity of the single question was 0.95 while sensitivity was 0.80 using the MDAS dichotomous classification. The single-item question related to age (p<0.001), gender (p<0.001), and dental attendance (p<0.001), as predicted. CONCLUSIONS: The single question has good validity, specificity, and sensitivity and may be used with confidence to assess dental fear in such situations as national health surveys or in routine dental practice where a multi-item dental anxiety questionnaire is not feasible.     

Distinct intraspecific variations of garlic (Allium sativum L.) revealed by the exon–intron sequences of the alliinase gene

Garlic (Allium sativum L.) has been used worldwide as a food and for medicinal purposes since early times. Garlic cultivars exhibit considerable morphological diversity despite the fact that they are mostly sterile and are grown only by vegetative propagation of cloves. Considerable recombination occurs in garlic genomes, including the genes involved in secondary metabolites. We examined the genomic DNAs (gDNAs) from garlic, encoding alliinase, a key enzyme involved in organosulfur metabolism in Allium plants. The 1.7-kb gDNA fragments, covering three exons (2, 3, and 4) and all four introns, were amplified from total DNAs prepared from garlic samples produced in Asia and Europe, leading to 73 sequences in total: Japan (JPN), China (CHN), India (IND), Spain (ESP), and France (FRA). The exon sequences were highly conserved among all the sequences, probably reflecting the fully functional alliinase associated with the flavor quality. Distinct intraspecific variations were detected for all four intron sequences, leading to the haplotype classifications. A close relationship between JPN and CHN was observed for all four introns, whereas IND showed a more divergent distribution. ESP and FRA afforded clearly different variants compared with those from Asian sequences. The present study provides information that could be useful in the development of an additional molecular marker for garlic authentication and quality control.     

Dipeptidyl Peptidase-4 Inhibitor (Vildagliptin) Improves Glycemic Control After Meal Tolerance Test by Suppressing Glucagon Release

Aim

We aimed to evaluate changes in insulin and glucagon secretion, as well as glucose levels, with a meal tolerance test (MTT) before and after 6 months of treatment with vildagliptin in a clinical setting.

Materials and Methods

Participants were 15 patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA_1c] over 6.9 % for more than 3 months). MTTs were conducted before and 6 months after addition of vildagliptin (50 mg twice daily [bid]). Blood samples were collected immediately before, and 1 and 2 h after the test meal for measurement of blood glucose concentration, immune-reactive insulin (IRI), and glucagon. HbA_1c was measured at 6 months.

Results

Mean age of participants was 55.5 ± 2.8 years, and ten (66.7 %) were male. Mean HbA_1c significantly improved from 7.6 to 6.8 % at 6 months after addition of vildagliptin. Blood glucose at 1 and 2 h after the test meal was significantly reduced after addition of vildagliptin, while the reduction in glucagon showed borderline significance and IRI showed no difference. In a comparison of blood glucose-related parameters between subgroups based on median glucose change in area under the curve during MTT (ΔAUC_0–2h), glucagon ΔAUC_0–2h was significantly lower in the group with more improved glucose levels (ΔAUC_0–2h ≥65 mg/dL), but that of IRI did not differ.

Conclusion

Suppression of glucagon release by vildagliptin may improve glycemic control without increasing insulin levels in patients with type 2 diabetes.     

Sustained elevation of extracellular dopamine causes motor dysfunction and selective degeneration of striatal GABAergic neurons

Dopamine is believed to contribute to the degeneration of dopamine-containing neurons in the brain. However, whether dopamine affects the survival of other neuronal populations has remained unclear. Here we document that mice with persistently elevated extracellular dopamine, resulting from inactivation of the dopamine transporter gene, sporadically develop severe symptoms of dyskinesia concomitant with apoptotic death of striatal dopamine-responsive gamma-aminobutyric acidergic neurons. Chronic inhibition of dopamine synthesis prevents the appearance of motor dysfunction. The neuronal death is associated with overactivation of dopaminergic signaling as evidenced by the robust up-regulation of striatal DeltaFosB, cyclin-dependent kinase 5, and p35. Moreover, hyperphosphorylation of the tau protein, a phenomenon associated with the activation of cyclin-dependent kinase 5 in several neurodegenerative disorders, is observed in symptomatic mice. These findings provide in vivo evidence that, in addition to its proposed role in the degeneration of dopamine neurons, dopamine can also contribute to the selective death of its target neurons via a previously unappreciated mechanism.     

Role of sphingosine-1-phosphate phosphohydrolase 1 in the regulation of resistance artery tone

Sphingosine-1-phosphate (S1P), which mediates pleiotropic actions within the vascular system, is a prominent regulator of microvascular tone. By virtue of its S1P-degrading function, we hypothesized that S1P-phosphohydrolase 1 (SPP1) is an important regulator of tone in resistance arteries. Hamster gracilis muscle resistance arteries express mRNA encoding SPP1. Overexpression of SPP1 (via transfection of a SPP1(wt)) reduced resting tone, Ca2+ sensitivity, and myogenic vasoconstriction, whereas reduced SPP1 expression (antisense oligonucleotides) yielded the opposite effects. Expression of a phosphatase-dead mutant of SPP1 (SPP1(H208A)) had no effect on any parameter tested, suggesting that catalytic activity of SPP1 is critical. The enhanced myogenic tone that follows overexpression of S1P-generating enzyme sphingosine kinase 1 (Sk1(wt)) was functionally antagonized by coexpression with SPP1(wt) but not SPP1(H208A). SPP1 modulated vasoconstriction in response to 1 to 100 nmol/L exogenous S1P, a concentration range that was characterized as S1P2-dependent, based on the effect of S1P(2) inhibition by antisense oligonucleotides and 1 mumol/L JTE013. Inhibition of the cystic fibrosis transmembrane regulator (CFTR) (1) restored S1P responses that were attenuated by SPP1(wt) overexpression; (2) enhanced myogenic vasoconstriction; but (3) had no effect on noradrenaline responses. We conclude that SPP1 is an endogenous regulator of resistance artery tone that functionally antagonizes the vascular effects of both Sk1(wt) and S1P2 receptor activation. SPP1 accesses extracellular S1P pools in a manner dependent on a functional CFTR transport protein. Our study assigns important roles to both SPP1 and CFTR in the physiological regulation of vascular tone, which influences both tissue perfusion and systemic blood pressure.     

Typhoid fever as a rare cause of hepatic, splenic, and bone marrow granulomas

During the course of typhoid fever, the usual histologic finding of the liver is "nonspecific reactive hepatitis." Hepatic granuloma (HG) is a rare complication of typhoid fever. We present two cases of typhoid fever with HG and review the relevant literature. Case 1 (a 53-year-old female) was found to have both hepatic and splenic granulomas. This is the first case of typhoid fever with splenic granulomas in the English language literature. Case 2 (a 66-year-old male) developed granulomas in the bone marrow in addition to HG. It should be considered that typhoid fever may lead to granulomas in several organs.     

Non-enhanced magnetic resonance angiography can evaluate restenosis after carotid artery stenting with the Carotid Wallstent

Background

Carotid artery stenting (CAS) requires follow-up imaging to assess in-stent restenosis (ISR). This study aimed to determine whether non-enhanced magnetic resonance angiography (NE-MRA) is useful for evaluating ISR.

Method

Between 2009 and 2013, we performed 118 consecutive CAS procedures using the Precise stent (n?=?78) and the Carotid Wallstent (n?=?40). We reviewed 1.5 T NE-MRA and examined visualization of the stent lumen and the degree of ISR if present. Other imaging modalities were used as references.

Results

NE-MRA performed just after CAS was not able to visualize the stent lumen in all patients because of metal artifacts. In the Carotid Wallstent group, follow-up NE-MRA was available in 22 patients. The stent lumen was visible more than three months after CAS in all patients. Among them, >40 % ISR was observed by other modalities in eight lesions. The degree of restenosis measured by NE-MRA (y%) had a linear relationship with that measured by conventional angiography (x%) (y?=?0.97x-0.4, r?=?0.79, P?=?0.021). In one case among 17 without ISR (6 %), NE-MRA showed false ISR. In the Precise stent group, NE-MRA did not visualize the stent lumen in the follow-up period.

Conclusions

NE-MRA can visualize the stent lumen in the Carotid Wallstent more than three months after CAS, but not in the Precise stent at follow-up. This delayed visualization might depend on endothelialization of the stent lumen. The degree of ISR measured by NE-MRA is comparable to that by conventional angiography. NE-MRA can evaluate ISR after CAS with the Carotid Wallstent (100 % sensitivity and 94 % specificity).