'Vitamin D and cognition in older adults': updated international recommendations.

BACKGROUND: Hypovitaminosis D, a condition that is highly prevalent in older adults aged 65 years and above, is associated with brain changes and dementia. Given the rapidly accumulating and complex contribution of the literature in the field of vitamin D and cognition, clear guidance is needed for researchers and clinicians. METHODS: International experts met at an invitational summit on 'Vitamin D and Cognition in Older Adults'. Based on previous reports and expert opinion, the task force focused on key questions relating to the role of vitamin D in Alzheimer's disease and related disorders. Each question was discussed and voted using a Delphi-like approach. RESULTS: The experts reached an agreement that hypovitaminosis D increases the risk of cognitive decline and dementia in older adults and may alter the clinical presentation as a consequence of related comorbidities; however, at present, vitamin D level should not be used as a diagnostic or prognostic biomarker of Alzheimer's disease due to lack of specificity and insufficient evidence. This population should be screened for hypovitaminosis D because of its high prevalence and should receive supplementation, if necessary; but this advice was not specific to cognition. During the debate, the possibility of 'critical periods' during which vitamin D may have its greatest impact on the brain was addressed; whether hypovitaminosis D influences cognition actively through deleterious effects and/or passively by loss of neuroprotection was also considered. CONCLUSIONS: The international task force agreed on five overarching principles related to vitamin D and cognition in older adults. Several areas of uncertainty remain, and it will be necessary to revise the proposed recommendations as new findings become available.

Changes in liquid emptying in migraine patients: diagnosed with liquid phase gastric emptying scintigraphy.

Gastric stasis is suspected mostly to be encountered during acute migraine attack. The aim of this study is to evaluate the liquid phase gastric emptying and motility in migraine patients in ictal and interictal periods in comparison to normal subjects with gastric emptying scintigraphy. Seven women with migraine and age, sex matched controls who applied to the Neurology Department from May 2009 to May 2010 were compared. Gastric emptying study with a standard liquid was performed one time in the non-migraineur group and two times in the migraineur group. Non-migraineur controls and migraineurs were compared. The mean T1/2 was longer in ictal period in migraineurs. The T1/2 of migraineurs interictally and the control groups were similar. The T1/2 of migraineurs ictally and migraineurs interictally were also compared. We also considered the percentage of the radioactive material remaining in the stomach. There were no significant differences between non-migraineurs and migraineurs interictally. However, increased amount of radioactive material remaining in the stomach was observed in migraineurs ictally. We concluded that the liquid emptying was delayed in spontaneous migraine attacks in migraine without aura, however in the interictal period the emptying of liquids did not differ between migraineurs and non-migraineurs.

Effect of an oral anxiolytic medication and heart rate variability on image quality of 64-slice MDCT coronary angiography.

PURPOSE: The aim of the study was to investigate the relationship between image quality in 64-slice multidetector computed tomography (MDCT) and patients' preimaging anxiety status and heart rate variability (HRV), and to evaluate the efficacy of an orally administered anxiolytic medication on HRV and image quality. MATERIALS AND METHODS: Sixty patients [14 women, 46 men; mean age 52.53 ± 10.55 (SD), range 33-78 years] were studied. Anxiety levels were assessed with the State-Trait Anxiety Inventory 60 min before the procedure. The participating patients were randomly assigned to one of the two study groups: a control group (no medication administered for anxiety reduction) and an anxiolytic medication group, with 30 patients in each group. The presence of motion artefacts and image quality for each coronary artery segment were evaluated using a four-point grading system. To estimate HRV, the duration of each heartbeat during MDCT data acquisition was measured in each patient. RESULTS: A moderate correlation was found between HRV during MDCT scanning and the mean image quality for all coronary segments (r=0.47, p<0.01). There was an association between HRV and state anxiety scores in all cases (r=0.370, p<0.01). HRV in the patients who received alprazolam was statistically significantly lower than in controls (p<0.05). The average image quality in patients who used alprazolam was also statistically significantly higher than in controls (p<0.05). CONCLUSIONS: The most important finding in our study is that oral premedication to reduce anxiety is also effective in decreasing HRV and improves image quality. Therefore, we suggest that using alprazolam in addition to a ß-blocker may improve image quality in patients undergoing MDCT coronary angiography (MDCT-CA). Anxiolytic usage may improve image quality by lowering the HRV in selected cases where administration of a ß-blocker is contraindicated. We also suggest that further studies in larger series are required to validate this finding.

Peripheral nervous system involvement in patients with sickle cell disease.

BACKGROUND AND PURPOSE: Peripheral nervous system involvement is rare in sickle cell disease (SCD). The aim of this study is to determine the peripheral nerve involvement electrophysiologically in SCD patients without clinically evident neurological signs, symptoms and to determine the relationship between the frequency of sickle cell crisis and peripheral neuropathy. METHODS: Fifty-one patients with SCD and fifty-one healthy controls were enrolled to the study. Conventional electrophysiological studies of peripheral nerves were performed to all subjects. The data about the frequency of sickle cell crisis were obtained. RESULTS: Peripheral nervous system involvement was detected in ten (19.6%) patients. Five (9.8%) patients had sensorimotor axonal neuropathy, two (3.9%) sensory axonal neuropathy, one (2%) patient had ulnar sensory neuropathy and two (3.9%) had median sensory neuropathy. Sural nerve sensorial action potential was unobtainable in eight (15.7%) patients and prolonged F latencies were observed in three (5.9%). The frequency of neuropathy was higher in SCD patients when compared with the controls. The frequency of sickle cell crisis was not significantly correlated with peripheral neuropathy. CONCLUSION: Subclinical peripheral nerve involvement may be seen in SCD patients. Electrophysiological examinations are recommended in routine examination to diagnose early neuropathy in SCD patients without neurologic symptoms.

Cerebral venous thrombosis in Behçet's disease compared to those associated with other etiologies.

Cerebral venous thrombosis (CVT) is caused by various etiologies. In Mediterranean and Middle Eastern countries, Behçet's disease (BD) is one of the leading causes of CVT. We aimed to evaluate any differences in CVT patients with and without BD. All registered patients with CVT were evaluated retrospectively. Clinical, neuroradiological findings and follow-up data were compared between patients with BD and patients with other etiologies. There were 36 patients with CVT and BD, and 32 patients with CVT related to other etiological causes. BD patients were younger (median age at onset 26 vs. 39 years; P < 0.001), and there was a male preponderance (28 males, 8 females) as compared to the non-BD group (10 males, 22 females; P < 0.001). Onset was frequently acute in the non-BD group, and it was subacute or chronic in the BD group. Hemi/quadriparesis, aphasia and seizures were significantly more common (P < 0.001) in the non-BD group. In the BD group 94% of the patients presented with symptoms of isolated intracranial hypertension (P < 0.001). Venous infarcts were observed in 63% of the patients with other causes and in 6% of the patients with BD (P < 0.001). At admission 97% of the patients in the BD group and 41% of the patients in the non-BD group had a modified Rankin score of 0-2. Outcome was good in all of the patients with BD and in 91% of patients with other causes. Clinical recurrences were seen in six patients with BD and in one patient without BD. CVT associated with BD has a subacute onset, mostly presents with signs of isolated intracranial hypertension and venous infarction rarely develops; these features distinguish CVT due to BD from those with other causes.

The effects of 5-aminoimidazole-4-carboxamide riboside on the pancreas in neonatal streptozotocin-diabetic rats.

In this study, we aimed to determine the alterations of beta-cell ultrastructure, insulin mRNA and protein products of the same gene on the pancreas of rats following long-term treatment of 5-aminoimidazole-4-carboxamide riboside (AICAR). A single dose of streptozotocin (STZ) 100 mg/kg was injected intraperitoneally (i.p.) to 2-day-old newborn (n2) rats. The rats were divided into three groups. The first group was the n2 STZ-diabetic rats. The second group consisted of n2 STZ-diabetic rats treated with AICAR 10 mg/kg/day for one month. The third group was non-diabetic control rats. Our findings demonstrate that AICAR treatment decreases the blood glucose level but increases the body weight in n2 STZ-diabetic rats. In the AICAR-treated group, numerous beta cells showed increased insulin gene expression. We also observed increased exocytosis in this group, in an ultrastructural manner. As a result, it is suggested that AICAR may induce insulin synthesis and betacell regeneration in n2 STZ-diabetic rats.

Apolipoprotein E polymorphism in Turkish subjects with Type 2 diabetes mellitus: allele frequency and relation to serum lipid concentrations.

The role of apolipoprotein E (apoE) genotypes in modulating plasma lipid and apolipoprotein levels was studied in 112 patients with Type 2 diabetes mellitus (T2DM) and 94 healthy individuals. ApoE genotypes were identified by PCR amplification and subsequent restriction endonuclease digestion. The apoE allele and genotype frequencies were similar in both the diabetic and control subjects. The apoE allele frequencies were found to be 74.3 for e3, 10.1 for e2, 15.6 for e4 in the diabetic group, and 68.1 for e3, 13.2 for e2 and 18.7 for e4 in the control group. Sex-specific genotypic distribution of apoE polymorphism did not differ between the study groups. To elucidate the association of apoE with lipid abnormalities with respect to gender, serum lipid and apolipoprotein levels were compared among apo e2 (e2/2 and e3/2), e3 (e3/3) and e4 (e4/3 and e4/4) groups of T2DM and control subjects. Apo e2 allele was found to be associated to triglycerides for both sexes, and associated to glucose, and BMI only in females. Subjects with e2 allele had higher levels of BMI, glucose and triglyceride in comparison to e3 and e4. Our data suggest that genetic variation at the apoE locus in Turkish subjects is a genetic factor that influences lipid levels. Further studies attempting to correlate apoE polymorphism with lipid profile in a large number of individuals would be helpful in establishing the true significance of this polymorphism in the Turkish population.

Effects of acid inhibition on somatostatin-producing cells in the rat gastric fundus.

Somatostatin plays a role in the regulation of gastric acid secretion. Omeprazole, a potent inhibitor of gastric acid secretion, has been reported to cause either a significant decrease or increase in the formation of gastric somatostatin-producing cells. Therefore, we determined in the present study distribution patterns of somatostatin mRNA and protein in fundus mucosa of rats after long-term inhibition of gastric acid secretion. Female Sprague-Dawley rats were given 0, 20 and 100 mg/kg/day omeprazole, respectively, as gastric instillations during 2 months. Serum gastrin levels were significantly higher in the third group than in the other groups. The omeprazole-treated groups also showed an increase in the number of somatostatin-containing cells in fundus mucosa. Moreover, the intensity of somatostatin-positivity was higher in the treated groups than in the control group. We also observed an increase in the number of cells containing somatostatin mRNA in fundus mucosa of omeprazole-treated rats. These results suggest that long-term inhibition of acid secretion does not inhibit but stimulate somatostatin production in mucosa of rat gastric fundus.

Detection of c-erbB-2 mRNAs using dig-labelled oligonucleotide probe with in situ hybridisation in human breast carcinoma: comparison with immunohistochemical results.

Amplification and overexpression of the c-erbB-2 oncogene are of prognostic significance in human breast cancer. Overexpression of c-erbB-2 is the result of gene amplification. However, increased transcript levels of c-erbB-2 are also detected in the absence of gene amplification. In this study for the detection of the overexpression mRNA in situ hybridisation (ISH) and immunohistochemistry (IHC) were used. Our aim was to develop the suitable mRNA ISH protocol for formalin-fixed paraffin-embedded material and to compare the localisation of transcripts and protein products in 20 primary breast carcinomas. Sections were immunostained with monoclonal c-erbB-2 antibody. In ISH method digoxigenin-labelled oligoprobe was used for the detection of c-erbB-2 mRNAs. We determined optimal condition for the ISH procedure (e.g., probe concentration, digestion, post washing). c-erbB-2 protein overproduction was detected in 11/20 cases with IHC. The mRNA signals were observed in malignant cell cytoplasm in 6/20 cases by ISH. ISH positive signals were found in only one case without detected overexpression of the protein. There were cell to cell variations in the hybridisation signals even within individual tumours. The ISH and IHC positive signals for c-erbB-2 was observed mostly in infiltrating ductal carcinomas that belong to aggressive lesions.

Alterations in gastrin cells induced by short-term omeprazole treatment in the rat antrum: an immunocytochemical and in situ hybridization study.

Gastrin is a hormonal regulator of gastric acid secretion and a trophic stimulant of acid-producing gastric mucosa. The blockage of acid secretion has been reported to cause hypergastrinaemia and gastrin cell hyperplasia. These findings suggest that achlorhydria may stimulate gastrin gene expression in gastrin cells. In this study, we aimed to determine the alterations of gastrin mRNA by non-radioactive in situ hybridization, and also to compare the localization of transcripts and protein products of the same gene by immunocytochemistry in an acid inhibition environment provided by omeprazole. Female Sprague-Dawley rats, weighing 200-250 g, were divided into three groups. The first group was the control group (eight rats). The second group (eight rats) was given 20 mg kg-1 day-1 omeprazole as intragastric instillations for 4 days. The third group (eight rats) was given 100 mg kg-1 day-1 omeprazole as in the second group. Serum gastrin levels in the two groups treated with omeprazole showed a statistically significant increase (P < 0.001) compared with the control group. The omeprazole-treated groups also showed an increase in the number of immunoreactive gastrin cells in the pyloric mucosa and an enhancement in the intensity of immunoreaction. Cells containing gastrin mRNA signals were observed in the upper regions of the pyloric glands in the pyloric sections of the control group and in both experimental groups.

Combined non-radioactive detection of peptide hormones and their mRNAs in stomach somatostatin cells.

Non-radioactive in situ hybridization (ISH) and immunocytochemistry (ICC) have been used to detect somatostatin (SS) messenger RNA (mRNA) and peptide in antropyloric mucosa of the stomach in the rats. We have applied a method of non-radioactive in situ hybridization histochemistry using digoxigenin labelled oligonucleotide probes to detect somatostatin gene expression in the stomach. In prehybridization stage we used proteinase K (PK) in various concentrations (from 1 to 10 micrograms/ml) and periods (from 10 min to 1 h) but we maintained high background. However it was possible to detect the somatostatin mRNAs in the stomach mucosa making use of either background preventing solutions during the prehybridization, or of levamisole (20 microliters/mg) added into the hybridization buffer or of pepsin. Somatostatin mRNA and peptide signals were scattered all through the mucosa especially localized particularly at the base of the pyloric glands. SS peptide shown by ICC and SS mRNA shown by ISH were observed in different cells.

[Lipoid proteinosis in 2 sisters]. / Lipoidproteinose bei zwei Schwestern.

Lipoid proteinosis was diagnosed in two daughters of a consanguinous marriage on the basis of genetic, clinical, light microscopic and ultrastructural findings. Hyaline material accumulation, thickening of the basal laminae and the resulting typical onion skin phenomenon were observed. In addition to the pathognomonic cutaneous mucosal findings, unusual manifestations such as persistence of deciduous teeth (in one case), oligodontia and intracerebral calcifications were observed. In one patient, the intracerebral calcifications caused epileptic seizures.

HLA antigens in recurrent oral ulceration: evidence against a common disease spectrum with Behçet's syndrome.

Among 50 patients with recurrent oral ulceration (ROU) the prevalence of HLA B5 was not increased as was the case among 50 patients with Behçet's Syndrome (BS) compared to 52 healthy controls. On the other hand, HLA DR4 was present in 16 of 30 (53%) patients with ROU whereas the same allele was present in 16% of BS patients and 22% of the healthy controls. These findings suggest that ROU and BS are not in the same disease spectrum.