IntroductionParkinson’s disease (PD) is characterized by the accumulation of abnormal α-synuclein in selected regions of the brain following a gradient of severity with disease progression. Whether this is accompanied by globally altered protein synthesis is poorly documented. The present study was carried out in PD stages 1-6 of Braak and middle-aged (MA) individuals without alterations in brain in the substantia nigra, frontal cortex area 8, angular gyrus, precuneus and putamen.ResultsReduced mRNA expression of nucleolar proteins nucleolin (NCL), nucleophosmin (NPM1), nucleoplasmin 3 (NPM3) and upstream binding transcription factor (UBF), decreased NPM1 but not NPM3 nucleolar protein immunostaining in remaining neurons; diminished 18S rRNA, 28S rRNA; reduced expression of several mRNAs encoding ribosomal protein (RP) subunits; and altered protein levels of initiation factor eIF3 and elongation factor eEF2 of protein synthesis was found in the substantia nigra in PD along with disease progression. Although many of these changes can be related to neuron loss in the substantia nigra, selective alteration of certain factors indicates variable degree of vulnerability of mRNAs, rRNAs and proteins in degenerating sustantia nigra. NPM1 mRNA and 18S rRNA was increased in the frontal cortex area 8 at stage 5-6; modifications were less marked and region-dependent in the angular gyrus and precuneus. Several RPs were abnormally regulated in the frontal cortex area 8 and precuneus, but only one RP in the angular gyrus, in PD. Altered levels of eIF3 and eIF1, and decrease eEF1A and eEF2 protein levels were observed in the frontal cortex in PD. No modifications were found in the putamen at any time of the study except transient modifications in 28S rRNA and only one RP mRNA at stages 5-6. These observations further indicate marked region-dependent and stage-dependent alterations in the cerebral cortex in PD. Altered solubility and α-synuclein oligomer formation, assessed in total homogenate fractions blotted with anti-α-synuclein oligomer-specific antibody, was demonstrated in the substantia nigra and frontal cortex, but not in the putamen, in PD. Dramatic increase in α-synuclein oligomers was also seen in fluorescent-activated cell sorter (FACS)-isolated nuclei in the frontal cortex in PD.ConclusionsAltered machinery of protein synthesis is altered in the substantia nigra and cerebral cortex in PD being the frontal cortex area 8 more affected than the angular gyrus and precuneus; in contrast, pathways of protein synthesis are apparently preserved in the putamen. This is associated with the presence of α-synuclein oligomeric species in total homogenates; substantia nigra and frontal cortex are enriched, albeit with different band patterns, in α-synuclein oligomeric species, whereas α-synuclein oligomers are not detected in the putamen.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-015-0257-4) contains supplementary material, which is available to authorized users.

Altered mitochondrial function is characteristic in the substantia nigra in Parkinson's disease (PD). Information about mitochondria in other brain regions such as the cerebral cortex is conflicting mainly because most studies have not contemplated the possibility of variable involvement depending on the region, stage of disease progression and clinical symptoms such as the presence or absence of dementia. RT-qPCR of 18 nuclear mRNAs encoding subunits of mitochondrial complexes and 12 mRNAs encoding energy metabolism-related enzymes; western blotting of mitochondrial proteins; and analysis of enzymatic activities of complexes I, II, II, IV and V of the respiratory chain were assessed in frontal cortex area 8 and the angular gyrus of middle-aged individuals (MA), and those with incidental PD (iPD), long-lasting PD with parkinsonism without dementia (PD) and long-lasting PD with dementia (PDD). Upregulation of several genes was found in frontal cortex area 8 in PD when compared with MA and in the angular gyrus in iPD when compared with MA. Marked down-regulation of genes encoding mitochondrial subunits and energy metabolism-related enzymes occurs in frontal cortex but only of genes coding for energy metabolism-related enzymes in the angular gyrus in PDD. Significant decrease in the protein expression levels of several mitochondrial subunits encoded by these genes occurs in frontal cortex area 8 and angular gyrus in PDD. Moreover, expression of MT-ND1 which is encoded by mitochondrial DNA is also reduced in PDD. Reduced enzymatic activity of complex III in frontal cortex area 8 and angular gyrus is observed in PD, but dramatic reduction in the activity of complexes I, II, II and IV in both regions characterizes PDD. Dementia in the context of PD is linked to region-specific deregulation of genomic genes encoding subunits of mitochondrial complexes and to marked reduction in the activity of mitochondrial complexes I, II, III and IV. INTRODUCTIONParkinson's disease (PD) is a chronic, progressive neurodegenerative disorder which in typical cases starts in the autonomic nervous system and olfactory bulb and then progresses to the medulla oblongata, pons and midbrain, and limbic system, eventually involving the neocortex several years after the beginning of symptoms. The classification of disease progression into six stages is based on the presence of the hallmark pathological lesions and is useful to explain clinical manifestations which parallel neuropathological lesions in typical cases, at least at the first and middle stages of the disease (8,14,15,27). Hallmark pathological lesions are Lewy bodies and neurites (LB inclusions) composed of abnormal a-synuclein (28).Altered mitochondrial function mainly characterized by reduced complex I activity and increased oxidative damage is well

Epidemiologic studies from South Asian countries have reported vitamin D deficiency among all age groups. However, there is very little information on vitamin D levels, especially in the vulnerable populations (pregnant/breast feeding mother and infants) in Sri Lanka. More data on vitamin D status of such populations will be important for policy decisions to be made at a national level. Similarly, it will be valuable for healthcare programs in other countries (e.g., United States, Australia, Europe, and Canada) as Sri Lankans are a fast-growing migrant population to those countries. The purpose of this study was to investigate maternal vitamin D status and its effects on infants in a state sector tertiary care centre in Sri Lanka. This prospective cohort study was conducted on 140 healthy pregnant mothers in the third trimester (mean gestational age 39±1 weeks). Blood was collected for 25(OH)D and parathyroid hormone (PTH). Sun exposure and feeding patterns of the infants were recorded based on maternal reporting. Mean age of the infants at follow-up visit was 36±7 days. Vitamin D (25 (OH)D) deficiency (<25 nmol/L) was observed in 12% pregnant mothers, 5% lactating mothers, and 63% infants. Insufficiency (<50 nmol/L) was found in an additional 51% and 43% in pregnant and lactating mothers and 25% of infants. Mean 25(OH)D was higher in pregnant (46.4±17.5 nmol/L) and lactating (51.9±17.0 nmol/L) mothers than infants (28.1±13.7 nmol/L). Maternal vitamin D level during pregnancy was a significant risk factor (OR: 6.00, 95%CI: 1.522-23.655) for infant deficiency and insufficiency. Sun exposure of infants showed a significant positive correlation with vitamin D level (OR: 3.23, 95%CI: 1.19-8.68). In conclusion, the presence of Vitamin D deficiency/insufficiency is higher in infants compared to pregnant/lactating mothers. Low maternal 25(OH)D during pregnancy was a risk factor for deficiency in infants. Although majority of lactating mothers had sufficient vitamin D, most of their exclusively breastfed offspring were deficient.

Introduction: Many studies from the Asian region have shown the existence of vitamin D deficiency among pregnant and breast feeding mothers despite abundant sunlight. Yet, we have little information on this topic in Sri Lanka. There are many skeletal and non-skeletal effects of vitamin D deficiency. Objectives: To investigate vitamin D status of pregnant mothers and its effect on growth parameters of the offspring. Method: We recruited 91 mothers who did not receive vitamin D supplementation during their pregnancy. 25(OH) D, parathyroid hormone (PTH), alkaline phosphatase, calcium and inorganic phosphorus levels were measured during the third trimester. Weight, length and head circumference (HC) of the babies were measured at birth and at one month of age. Results: Vitamin D deficiency (<10ng/ml) was present in 18.8% and insufficiency (10-20ng/ml) in 47.5%. This study showed no significant correlation between maternal vitamin-D levels and neonatal anthropometry (height, weight and head circumference). Conclusions: A significant rate of vitamin D deficiency was observed in pregnant mothers. There was no correlation between maternal vitamin-D levels and neonatal anthropometry in this study.

Results of various studies have shown severe vitamin D deficiency in the Indian subcontinent in all age groups and insufficiency in populations of SouthEast and East Asia. There are no data available in Sri Lanka on vitamin D status in pregnant mothers. Vitamin D supplements are not provided routinely in state sector clinics. Institute of Medicine of the National Academy of Sciences in the USA recommends safe upper limit of dietary vitamin D as 4000 IU. Our aim of this study was to assess vitamin D status and adequacy of vitamin D intake through diet among pregnant mothers. This is a secondary analysis of data of a prospective cohort study. 89 pregnant mothers in their 3rd trimester were recruited. Food frequency questionnaire based on 7-day estimated food record method was used. Analysis of blood sample was done for vitamin D, parathyroid hormone (PTH), calcium, inorganic phosphorous and alkaline phophatase levels.Statistical analysis used Spearman's correlation and independent sample t-test were performed. We found that 12.4%, 50.6% and 37.1% were vitamin D deficient, insufficient and sufficient respectively. 25(OH)D and PTH showed a significant negative correlation (r=0.296; P<0.01). Yet, serum PTH level was above the cutoff only among 4.5%. Further, only 13.5% subjects had high ALP (>240 IU/L). Average daily intake of vitamin D through diet was 1289.4 ± 1225.6 IU/day (range 56 IU-5400 IU). Significant Main source of vitamin D was fortified milk powder and small fish.. High rate of vitamin D insufficiency/deficiency was observed and this novel finding in our cohort suggests investigating vitamin D status in pregnant mothers at a national level. Vitamin D intake through diet was not adequate in our study sample. Further, rigorous trails are needed to evaluate the requirement for supplementation to optimise the bone metabolism during pregnancy in Sri Lanka.

A descriptive cross-sectional study, Level V.

Central obesity is a significant risk factor for metabolic syndrome in adults. Central fat distribution greatly alters the lipid profile and induces atherogenic dyslipidaemia even in normoglycaemic, non-hypertensive subjects. Hence, the aim of the present study was to identify the serum lipid parameters which are altered with central obesity in non-diabetic, non-hypertensive subjects in Sri Lanka. A cross-sectional study was conducted at the Family Practice Centre of University of Sri Jayewardenepura, after obtaining ethical clearance and informed written consent from 227 non-diabetics, non-hypertensive subjects who were not on Statins. Overnight fasting venous blood was collected and assayed for serum lipid profile such as triglycerides (TG), total cholesterol (TC) and high density cholesterol (HDL). Low density cholesterol (LDL) and TG/HDL ratio were calculated. Waist circumference (WC) was measured based on WHO and NHANES standards. All data were analysed using SPSS (ver.17) software. Mean age of the subjects was 40.7 ± 13.7 years and 59.9% were females. Obese males and females were 40.7% and 49.3% respectively. In the study sample, mean TG and TG/HDL ratio were significantly (p<0.05) higher in obese males. However, all mean serum lipid parameters such as TG, TC, LDL and TG/HDL ratio were higher in both obese males and females and HDL was lower in them. Hence, even in non-diabetic, non-hypertensive subjects, central obesity has a relationship with altered lipid profile which could lead to obesity related metabolic abnormalities.

BACKGROUND : Acute cardiac complications in peripartum period provide a diagnostic challenge. Takatsubo cardiomyopathy occurs most frequently in postmenopausal women exposed to emotionalandphysicalstress. We report a case of apical ballooning syndrome, also known as Takotsubo Cardiomyopathy (TCM) or broken-heart syndrome, in a preeclamptic patient post operatively. CASE : 44 year preeclamptic primi presented with dyspnoea three hours after sub arachnoid block for caeserean. On evaluation, trans thoracic echo revealed apical ballooning with global hypokinesia along with raised NT-Pro BNP level. ECG and cardiac enzymes werenormal. She was intubated, ventilated and treated with inotropes and anti failure medications by a multidiciplinary team.She was extubated on Postoperativeday (POD) 3 and discharged on POD 13 with stable vitals. Her echo done on third month was completely normal with adequate left ventricular function. CONCLUSION : Physical, emotional stress and oestrogen deciency in immediate post partum period may be the predisposing risk factors for TCM even if regional anaesthesia is given. Trans thoracic echo plays a vital role in differenciating TCM from other peripartumcardiac complications like pulmonary thrombo embolism, peripartum cardimyopathy or acute coronary syndrome.