National response to neurological diseases in Malaysia: planning for the future

The number of cases of neurological disease is expected to rise in the next 10 years, making this the second leading cause of morbidity and mortality after heart disease in Malaysia. The lack of human resources in the neurological field currently serving the Malaysian population may cause a deficiency in specialized care, especially in rural areas where neurological and neurosurgical care may be lacking. Thus, a resolve was made to increase the numbers of specialists by the Universiti Sains Malaysia (USM) with the help of the Ministry of Health of Malaysia. A study was made to evaluate the number of referral centers needed in strategic parts of Malaysia. Our calculation was based on service demands and operative procedures following the guidelines of the Association of British Neurologists (ABN) where 15 minutes of service time was equivalent to 1 unit. Based on 2 million population covered in the state of Kelantan by this University Hospital, 4.27 neurologists are needed to meet service demands with a consultant to population ratio (CPR) of 1:468,384, compared to 7.46 neurosurgeons, with a CPR of 1:268,097. According to the current service demands, one neurologist has to work more than 407 hours per year and one neurosurgeon 1,219 hours per year in our hospital. Hospitals with a larger catchment area would need to have more neurologists and neurosurgeons for optimal care in their area. Thus, more neurologists and neurosurgeons are needed to be produced, since the existing numbers are too small for quality care in Malaysia.     

A novel technique to quantify the instantaneous mitral regurgitant rate

Background

The systolic variation of mitral regurgitation (MR) is a pitfall in its quantification. Current recommendations advocate using quantitative echocardiographic techniques that account for this systolic variation. While prior studies have qualitatively described patterns of systolic variation no study has quantified this variation.

Methods

This study includes 41 patients who underwent cardiovascular magnetic resonance (CMR) evaluation for the assessment of MR. Systole was divided into 3 equal parts: early, mid, and late. The MR jets were categorized as holosystolc, early, or late based on the portions of systole the jet was visible. The aortic flow and left ventricular stroke volume (LVSV) acquired by CMR were plotted against time. The instantaneous regurgitant rate was calculated for each third of systole as the difference between the LVSV and the aortic flow.

Results

The regurgitant rate varied widely with a 1.9-fold, 3.4-fold, and 1.6-fold difference between the lowest and highest rate in patients with early, late, and holosystolic jets respectively. There was overlap of peak regurgitant rates among patients with mild, moderate and severe MR. The greatest variation of regurgitant rate was seen among patients with mild MR.

Conclusion

CMR can quantify the systolic temporal variation of MR. There is significant variation of the mitral regurgitant rate even among patients with holosystolic MR jets. These findings highlight the need to use quantitative measures of MR severity that take into consideration the temporal variation of MR.     

Protein kinase C catalyzed phosphorylation of sterol carrier protein 2

The transport of cholesterol to the inner mitochondrial membrane, a key step in steroidogenesis, is subject to hormonal modulation that, at least in part, could be mediated by protein phosphorylation. This step is stimulated by sterol carrier protein 2 (SCP2) and Ca2+. To explore whether SCP2 itself is a potential control point for regulation by Ca2+-dependent phosphorylation we investigated whether highly purified SCP2 could serve as a substrate for major type Ca2+ and non-Ca2+-dependent protein kinases. Phosphorylation by calmodulin protein kinase II (CaM-PK II), myosin light chain kinase (MLCK), cAMP-dependent kinase (PKA) and protein kinase C (PKC) was monitored under optimal conditions for each enzyme. PKA, CaM-PK II and MLCK catalyzed the radiolabeling of histone 2A, synapsin I and myosin light chain (MLC), known substrates for these kinases, respectively, yet no phosphate transfer to SCP2 was observed. In contrast, PKC from two different sources (rat and calf brain) effectively catalyzed the phosphorylation of the highly purified SCP2. The phosphorylation of SCP2 depended on the addition of Ca2+ and phospholipids and was completely blocked by Polymyxin B, a PKC inhibitor. PKC catalyzed phosphorylation of SCP2 displayed a similar dependence on the concentration of ATP. Lineweaver Burk plots of the data indicate Km values for ATP of approximately 6 microM for the phosphorylation of SCP2. Our results, which have revealed for the first time that SCP2 is a substrate for PKC, are consistent with the possibilities that the control of steroidogenesis by tropic hormones and by PKC activation are mediated, at least in part, by the phosphorylation/dephosphorylation of SCP2.     

Interleukin-23 and its correlation with disease activity,joint damage,and functional disability in rheumatoid arthritis

The purpose of this study was to compare the serum interleukin (IL)-23 levels between rheumatoid arthritis (RA) patients and healthy controls and to determine the correlation of IL-23 levels with disease activity, joint damage and functional disability in RA. Serum samples were obtained from 45 patients with RA and 45 healthy controls. The enzyme-linked immunosorbent assay method was used for quantitative analysis of IL-23. All the RA patients were assessed for disease activity based on the 28-joint disease activity score, joint damage based on modified Sharp score, and functional ability using the Health Assessment Questionnaire–Disability Index. The mean serum IL-23 level was much higher among the RA patients (24.50 ± 13.98 pg/mL) compared to the controls (5.98 ± 3.40 pg/mL; p < 0.01). There was a significant positive relationship between IL-23 levels and disease activity and questionnaire scores (p = 0.003 and 0.020, respectively). On logistic regression analysis, IL-23 levels were significantly higher in patients with moderate to high disease activity (p = 0.008, odds ratio = 1.073, 95% confidence interval = 1.019–1.130) and patients with significant functional disability (p = 0.008, odds ratio = 1.085, 95% confidence interval = 1.021–1.153). RA patients have significantly higher levels of serum IL-23. The IL-23 levels correlate well with disease activity and functional disability but not with radiographic joint damage.     

Luteal cell 3-hydroxy-3-methylglutaryl coenzyme-A reductase activity and cholesterol metabolism throughout pregnancy in the rat

The objective of this study was to investigate changes in luteal cell cholesterol biosynthetic capacity, cholesterol accumulation, lipoprotein receptor activity, and in vivo steroidogenesis during pregnancy. Cholesterol biosynthetic capacity was assessed by measuring both the activity and the content of the rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase and by monitoring [14C]acetate incorporation into luteal sterols. The results showed that HMG-CoA reductase activity increased steadily during the first few days of pregnancy and reached a peak value on day 10. Subsequently, enzyme activity dropped precipitously and remained low until parturition. A parallel decline in the rate of conversion of 14C-labeled sterols was observed. Such changes in HMG-CoA reductase activity were not related to the phosphorylation/dephosphorylation state of the enzyme, but were due to a reduction in the amount of enzyme protein, as determined by the immunoblotting technique. Despite the highly active HMG-CoA reductase in the first half of pregnancy, very little cholesterol ester was stored, and serum progesterone concentrations were only about 50-75 ng/ml. However, from midpregnancy, the corpus luteum became capable of storing more cholesterol ester and producing more progesterone at a time when its ability to synthesize cholesterol declined. At this stage, luteal cells appear to shut off de novo synthesis and use principally exogenous cholesterol. To find out whether this is due to an increase in the number of high density lipoprotein (HDL) receptors, HDL-binding activity was determined in luteal cells throughout pregnancy. Whereas the Kd and the number of binding sites per mg protein were similar between days 6-18, the total content of HDL receptor increased markedly with the size of the corpus luteum. In summary, the present investigation indicates that pregnancy profoundly influences the ability of the corpus luteum to acquire, synthesize, and process the cholesterol substrate needed for steroidogenesis.     

GnRH action in rat anterior pituitary gland: regulation of protein, glycoprotein and LH synthesis.

The effect of synthetic GnRH on the synthesis of proteins and glycoproteins in the anterior pituitary and in vitro release of LH into the medium was studied. A maximal dose (25 ng/ml) of of synthetic GnRH caused optimum release of radioimmunoassayable LH into the medium after 2 h of incubation. A concomitant increase in cyclic AMP accumulation in the tissue and LH in the incubation medium was also observed under the influence of GnRH during different periods of incubation time. Incubation of the rat anterior pituitary with GnRH stimulated the incorporation of [3H] proline into acid precipitable proteins in a time- and dose-dependent manner, similar to radioimmunoassayable LH released into the medium. Similar results were obtained when pituitary was incubated with dibutyryl cyclic AMP. LH, in addition, enhanced the incorporation of [3H] glucosamine and [3H] amino acids mixture into acid-precipitable proteins suggesting that proteins including glycoproteins are synthesized by the rat anterior pituitary under the influence of GnRH. Approximately 10% of the radioactivity associated with proteins comigrated with radioimmunoassayable LH on the gels. GnRH also enhanced the incorporation of [3H] glucosamine and [3H] amino acid mixture into immunoprecipitable LH. The GnRH-induced incorporation of [3H] proline into anterior pituitary proteins was abolished by specific translation inhibitors.     

Results of five-year term perinatal care of a diabetic woman

Authors had retrospectively analysed basic exponents of perinatal care of 199 pregnant diabetic woman in years 1993-1997 hospitalised and delivered in The First Clinic of Obstetrics and Gynaecology in the town of Bytom. Our results were very similar to the other Referent Centres Of Technical Methods Bank Used in Diagnostic and Therapy of Diabetes: average gestation age 38 +/- 1 hbd, caesars sections percentage 53.4%, 5.5% of undelivered pregnancies, 0.5% of new-born delivered with multiple congenital defaults, 16.1% of macrosomies and 28.1% pre-term deliveries were noted. Disadvantage perinatal effects in diabetic women might be reduced very early diagnosis of diabetic and intensive biophysical and biochemical fatal care, which is strongly suggests by the authors.     

Co-localization of neurotransmitter immunoreactivities in putative nitric oxide synthesizing neurones of the cat brain stem

The distribution of nitric oxide producing neurones in the medulla oblongata of the cat was investigated using nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry, and nitric oxide synthase (NOS) immunohistochemistry. The pattern of staining obtained with both methods was found to be similar. Strongly diaphorase and NOS reactive neurones were present in the paramedian and lateral tegmental fields, including the regions occupied by the Al/C1 catecholamine cell groups, the nucleus ambiguus and lateral reticular nucleus, and in a number of sensory nuclei including the nucleus of the tractus solitarius and the dorsal column nuclei. The extent of co-localization of NADPH-diaphorase with a number of neuropeptides and neurotransmitters was investigated by combining NADPH-diaphorase histochemistry with immunocytochernisty for neuropeptide Y, somatostatin, glutamate, cholecystokinin and tyrosine hydroxylase. NADPH-diaphorase reaction product was observed in neurones immunoreactive for glutamate and somatostatin. These double-labelled cells were found in the paramedian region, lateral reticular field, the nucleus prepositus hypoglossi and in the rostral nucleus of the tractus solitarius. In the rostral ventrolateral medulla NADPH-diaphorase/somatostatin immunoreactive cells were found in the paragigantocellular nucleus. NADPHdiaphorase/glutamate immunoreactive cells overlapped the nucleus ambiguus, the lateral reticular nucleus and the A1/C1 catecholaminergic cell groups. In addition, a few NADPH-diaphorase/glutamate immunoreactive cells were found in the paraolivary area and gigantocellular tegmental field, in the external cuneate and infratrigerninal nuclei. The functional implications of the co-localization of nitric oxide with these neurotransmitters in areas of the medulla concerned with cardiovascular regulation is discussed.