Alzheimer's disease: Immunoreactivity of neurofibrillary tangles with anti-neurofilament and anti-paired helical filament antibodies

The origin of the paired helical filaments (PHP) that accumulate in human neurons during aging and in Alzheimer's disease and their relationship to normal neurofilaments remain unclear. The observation that a rabbit antiserum to highly enriched PHF fractions specifically labeled PHF in Alzheimer neurofibrillary tangles but showed no reaction with neurofilaments or other normal cytoskeletal proteins led us to compare this antiserum to two monoclonal antibodies, RT97 and BF10, previously found to cross-react with tangles and with the 210, 000 and 155, 000 mol. wt. neurofilament proteins, respectively. Both α-PHF serum and the neurofilament monoclonals strongly immunolabel almost all neurofibrillary tangles in Alzheimer cortical sections. Double-immunolabeling studies show that both reagents recognize the same tangles and usually show identical patterns of staining of intraneuronal fibrous material. Following prolonged extraction of cortex in sodium dodecyl sulfate, a step which removes normal neurofilaments but leaves PHF intact, almost all isolated tangles retain strong immunoreactivity with α-PHF serum at an intensity which is slightly reduced from that in cortical sections. In contrast, only a small number of isolated tangles are stained strongly by RT97 and BF10; most show much decreased or no reactivity with these monoclonal neurofilament antibodies. This differential immunoreactivity was confirmed by double-labeling studies. Tangles prepared under gentle extraction conditions show strong reactivity with α-PHF antibodies but again only a small number are strongly labeled by RT97 and BF10. We conclude that neurofibrillary tangles in Alzheimer's disease are heterogeneous as regards their filamentous content and contain both antigens cross-reacting with neurofilaments and antigens which are apparently unique to PHF and not shared with normal neurofilaments.     

Increased frequency of diabetes mellitus in patients with bullous pemphigoid: A case-control study

A case-control study was designed to assess the occurrence rate of primary diabetes mellitus (DM) in patients with bullous pemphigoid (BP) by retrospectively reviewing the records of our thirty histopathologically and immunopathologically proved cases of BP from the past 10 years. One hundred twenty patients were selected as controls, which included two names immediately before and two names immediately after each case of BP in our histopathology record book. The occurrence rate of primary DM prior to the administration of systemic corticosteroids was significantly higher in patients with BP than in the controls (20% and 2.5%, respectively; p = 0.004). Among patients over 50 years of age, this occurrence rate was again higher in patients with BP than in the controls (23% and 3.6% respectively; p = 0.02). This study suggests a higher than chance association of BP and primary DM.     

Performance comparison of neural network training algorithms in modeling of bimodal drug delivery

The major aim of this study was to model the effect of two causal factors, i.e. coating weight gain and amount of pectin-chitosan in the coating solution on the in vitro release profile of theophylline for bimodal drug delivery. Artificial neural network (ANN) as a multilayer perceptron feedforward network was incorporated for developing a predictive model of the formulations. Five different training algorithms belonging to three classes: gradient descent, quasi-Newton (Levenberg-Marquardt, LM) and genetic algorithm (GA) were used to train ANN containing a single hidden layer of four nodes. The next objective of the current study was to compare the performance of aforementioned algorithms with regard to predicting ability. The ANNs were trained with those algorithms using the available experimental data as the training set. The divergence of the RMSE between the output and target values of test set was monitored and used as a criterion to stop training. Two versions of gradient descent backpropagation algorithms, i.e. incremental backpropagation (IBP) and batch backpropagation (BBP) outperformed the others. No significant differences were found between the predictive abilities of IBP and BBP, although, the convergence speed of BBP is three- to four-fold higher than IBP. Although, both gradient descent backpropagation and LM methodologies gave comparable results for the data modeling, training of ANNs with genetic algorithm was erratic. The precision of predictive ability was measured for each training algorithm and their performances were in the order of: IBP, BBP>LM>QP (quick propagation)>GA. According to BBP-ANN implementation, an increase in coating levels and a decrease in the amount of pectin-chitosan generally retarded the drug release. Moreover, the latter causal factor namely the amount of pectin-chitosan played slightly more dominant role in determination of the dissolution profiles.     

Assay of ertapenem in human serum by high-performance liquid chromatography

Ertapenem is a new carbapenem with a broad spectrum of activity and an extended half-life, permitting once daily administration. Although high-performance liquid chromatography (HPLC) methods have been described for ertapenem, these are complex and involve column switching and thus this type of assay may not suitable for use in routine clinical microbiology laboratories. In this study we report a rapid, straightforward HPLC method for the detection of ertapenem in human serum.     

Validation of a school children addictive behaviors questionnaire

The aim was to develop and validate an addictive behaviors screening tool in school children. METHODOLOGY: A cross sectional study including a self administrated 223 item questionnaire developed in Arabic language. The questionnaire included identification of the student and seven life domains: school, family, addiction, relationships with peers, leisure and well being, risky behaviors and personality traits. N=854 high school children. of Monastir City. RESULTS: the questionnaire Alpha Cronbach's Coefficient ranged between 0.3 and 0.8. Only items with a coefficient higher than 0.6 were maintained in the final version. The time reliability by using the Bland and Altman method 15 days after the first measure showed a Pearson's coefficient of 0.81. Validity evaluated by principal components analysis led to 3 independent factors consisting respectively in 20, 4 and 3 well correlated items: family, school and risky behaviors. CONCLUSION: validated version of the questionnaire consisted in 102 items, easy to read and understand. This version doesn't require much time to be filled in and takes into consideration cultural particularities of the school children of Monastir. It could be considered as an interesting tool for both the assessment and the prevention of addictive behaviors in school.     

The status of biochemical parameters in varying degrees of vitamin D deficiency

Vitamin D (Vit D) is an essential element for the regulation of serum calcium, phosphate, and alkaline phosphatase (Alk Ph). Because the Vit D serum level is not usually measured directly, Vit D deficiency is diagnosed indirectly by changes in serum calcium, phosphate, and Alk Ph leves. The current study assessed the status of these biochemical parameters in subjects with different degrees of Vit D deficiency. We selected 1210 subjects, between 20 and 69 years old, randomly from the Tehran population. Subjects with diseases or medications that modified bone metabolism were excluded from the study. Serum 25(OH) D, calcium, phosphate, Alk Ph, and parathyroid hormone (PTH) levels were measured and the status of these biochemical parameters was compared in subjects with different degrees of Vit D deficiency. Vit D deficiency was diagnosed in 79.6% of the subjects. Different degrees of Vit D deficiency were classified as follows: group 1, severe; group 2, moderate; and group 3, mild. Serum PTH levels in the Vit D-deficient groups were significantly higher than that in group 4 (normal Vit D). Serum calcium and phosphate levels in groups 1 and 2 were significantly lower than those in groups 3 and 4. No significant difference was seen in serum Alk Ph in the groups with different degrees of Vit D deficiency. The sensivity for at least one biochemical variable (calcium, phosphorus, or Alk Ph) for the detection of severe, moderate, and mild Vit D deficiency was 24.2%, 13.8%, and 6%, respectively. When the serum 25(OH) D level was reduced to less than 25 nmol/l (groups 1 and 2), the effects of Vit D deficiency on calcium and phosphate levels were obvious. Therefore, the usual biochemical parameters (calcium, phosphate, Alk Ph) alone do not have sufficient sensitivity to detect mild deficiency of Vit D.     

The inefficacy of riboflavin against ultraviolet-induced carcinogenesis.

Flavins are reported to protect cellular DNA against UV irradiation injury in vitro. The possible photoprotective effects of riboflavin in vivo on UV-induced carcinogenesis were studied in three groups of HR-hairless mice. Group I served as control. Group II was painted daily with a 15 mg per ml solution of riboflavin. In Group III, drinking water was replaced with a 15 mg per ml solution of riboflavin in water. All three groups were simultaneously irradiated in a light box with two Westinghouse FS20 sunlamps from a distance of 30 cm for 5 min daily 6 days a week throughout the experiment. By the 11th month all surviving mice developed several histologically proven squamous cell carcinomas. The total numbers and times of onset of tumors did not vary in the three groups. Thus, no protective effect of massive amounts of riboflavin on ultraviolet-induced carcinogenesis in the hairless mouse could be demonstrated when such high dose rates of UV were used.     

Profile of Kangari cancer: a prospective study

Kangari, an earthenware brazier containing burning charcoal, is used for personal warming during the winter months by most of the people in Kashmir valley. Kangari is usually held close to the lower abdomen or in between the legs while squatting on the ground. The use of kangari is associated with development of skin cancer at the sites of prolonged exposure. In the present study 43 patients with Kangari cancer were analyzed prospectively with the objective of understanding their clinico-pathological profile and the response to various treatment modalities. Variables such as age, gender, grade, site of lesion etc., were evaluated for their prognostic significance.     

Neonatal circumcision reduces the incidence of asymptomatic urinary tract infection: a large prospective study with long-term follow up using Plastibell

ObjectiveTo evaluate the preventive effect of neonatal circumcision on urinary tract infection and the incidence of complications following neonatal circumcision using Plastibell.Materials and methodsA prospective study was carried out between 2004 and 2008. During this period, there were 3000 neonatal circumcisions. All of the cases were examined for any complications 1 week later, and occurrence of meatal stenosis was followed up to 15 months of age. In this group, urine analysis and culture was successfully performed four times for 2000 circumcised infants at 1.5, 3, 9 and 15 months. In the control group of 3000 uncircumcised infants, 1000 cases accomplished urine analysis and culture at the same designated intervals.ResultsA positive urine culture was observed in none of the circumcised cases and in 20 (2%) uncircumcised cases after obtaining a suprapubic bladder aspiration sample. The latter 20 infants were circumcised and follow-up cultures were negative in 17 cases. The overall complication rate in the circumcised group was 1.6%. The difference in frequency of urinary tract infection between the two groups was statistically significant (P < 0.0001).ConclusionNeonatal circumcision has few complications and reduces the incidence of asymptomatic urinary infection. It may be considered as a preventative health measure.