Anti-Cholinesterase Activity of Chalcone Derivatives: Synthesis, In Vitro Assay and Molecular Docking Study.

BACKGROUND: Chalcones, originated from natural product, have been broadly studied their biological activity against various proteins which at the molecular level, are responsible for the progress of the diseases in cancer (e.g. kinases), inflammation (oxidoreductases), atherosclerosis (cathepsins receptor), and diabetes (e.g. α-glucosidase). OBJECTIVE: Here we synthesize 10 chalcone derivatives to be evaluated their in vitro enzymatic inhibition activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). METHODS: The synthesis was carried out using Claissen-Schimdt condensation and the in vitro assay was conducted using Ellman Method. RESULTS: Compounds 2b and 4b demonstrated as the best IC50 of 9.3 µM and 68.7 µM respectively, towards AChE and BChE inhibition. Molecular docking studies predicted that this activity might be due to the interaction of the chalcones with important amino acid residues in the binding site of AChE such as SER200 and in that of BChE, such as TRP82, SER198, TRP430, TYR440, LEU286 and VAL288. CONCLUSION: Chalcone can be used as the scaffold for cholinesterase inhibitor, in particularly either fluorine or nitro group to be augmented at the para-position of Ring B, whereas the hydrophobic chain is necessary at the meta-position of Ring B.

The effects of inorganic chromium and brewer's yeast supplementation on glucose tolerance, serum lipids and drug dosage in individuals with type 2 diabetes.

OBJECTIVE: To study the effects of supplementation with organic and inorganic chromium on glucose tolerance, serum lipids, and drug dosage in type 2 diabetes patients, in the hope of finding a better and more economical method of control. METHODS: Seventy eight type 2 diabetes patients were divided randomly into two groups and given Brewer's yeast (23.3ug Cr/day), and CrCl3 (200ug Cr/day) sequentially with placebo in between, in a double blind cross-over design of four stages, each lasting 8 weeks. At the beginning and end of each stage, subjects were weighed, their dietary data and drug dosage recorded, and blood and urine samples were collected for analysis of glucose (fasting and 2 hour post 75g glucose load) fructosamine, triglycerides, total and HDL-cholesterol, and serum and urinary chromium. RESULTS: Both supplements caused a significant decrease in the means of glucose (fasting and 2 hour post glucose load), fructosamine and triglycerides. The means of HDL-cholesterol, and serum and urinary chromium were all increased. The mean drug dosage decreased slightly (and significantly in case of Glibenclamide) after both supplements and some patients no longer required insulin. No change was noted in dietary intakes or Body Mass Index. A higher percentage of subjects responded positively to Brewer's yeast chromium, which was retained more by the body, with effects on fructosamine, triglycerides, and HDL-cholesterol maintained in some subjects when placebo followed it, and mean urinary chromium remaining significantly higher than zero time mean. CONCLUSION: Chromium supplementation gives better control of glucose and lipid variables while decreasing drug dosage in type 2 diabetes patients. A larger scale study is needed to help decide on the convenient chemical form, and dosage required to achieve optimal response.

Subclinical diabetic neuropathy: a common complication in Saudi diabetics.

OBJECTIVE: To determine the prevalence of sub clinical diabetic neuropathy in Saudi diabetics and the risk factors associated with symptomatic diabetic neuropathy. METHODS: A prospective study of Saudi diabetics attending King Abdulaziz University Hospital out patient clinic from January 1998 until April 1999. Detailed information of each patients' age, sex, body mass index, type and duration of diabetes mellitus, mode of treatment, degree of blood glucose control, presence of hypertension, hyperlipidemia, smoking, family history of diabetes mellitus and hypertension were recorded. Patients were assessed for diabetic neuropathy using the Michigan Neuropathy Program. Patients who were asymptomatic and scored less than 2 on simple clinical examination were referred to a neurologist for a complete neurological examination and nerve conduction studies. RESULTS: A total of 237 patients were studied with a mean age of 54.19 years and mean duration of diabetes 10.6 years. Symptomatic diabetic neuropathy was present in 132 (56%) patients while subclinical neuropathy was present in 58 (57%) of asymptomatic patients. Old age, type II diabetes with long duration, poor control and smoking were risk factors associated with symptomatic diabetic neuropathy (p<0.001, p=0.09, p<0.001, p=0.04, p=0.08). CONCLUSION: Subclinical diabetic neuropathy is common. Early diagnosis is important for possible prevention of late neuropathic complications (foot ulcers and infections). Prolonged poorly controlled diabetes mellitus, old age and smoking are risk factors for symptomatic diabetic neuropathy. Meticulous blood glucose control is important for nerve function protection. Researches are urgently needed for satisfactory therapy.

Subclinical diabetic neuropathy. A common complication in Saudi diabetics.

OBJECTIVE: To determine the prevalence of sub clinical diabetic neuropathy in Saudi diabetics and the risk factors associated with symptomatic diabetic neuropathy. METHODS: A prospective study of Saudi diabetics attending King Abdulaziz University Hospital out patient clinic from January 1998 until April 1999. Detailed information of each patients` age, sex, body mass index, type and duration of diabetes mellitus, mode of treatment, degree of blood glucose control, presence of hypertension, hyperlipidemia, smoking, family history of diabetes mellitus and hypertension were recorded. Patients were assessed for diabetic neuropathy using the Michigan Neuropathy Program. Patients who were asymptomatic and scored less than 2 on simple clinical examination were referred to a neurologist for a complete neurological examination and nerve conduction studies. RESULTS: A total of 237 patients were studied with a mean age of 54.19 years and mean duration of diabetes 10.6 years. Symptomatic diabetic neuropathy was present in 132 (56%) patients while subclinical neuropathy was present in 58 (57%) of asymptomatic patients. Old age, type II diabetes with long duration, poor control and smoking were risk factors associated with symptomatic diabetic neuropathy (p<0.001, p=0.09, p<0.001, p=0.04, p=0.08). CONCLUSION: Subclinical diabetic neuropathy is common. Early diagnosis is important for possible prevention of late neuropathic complications (foot ulcers and infections). Prolonged poorly controlled diabetes mellitus, old age and smoking are risk factors for symptomatic diabetic neuropathy. Meticulous blood glucose control is important for nerve function protection. Researches are urgently needed for satisfactory therapy.

Current practice patterns and training status of selected graduates at the King Abdulaziz University College of Medicine, Saudi Arabia.

Graduate doctors are the primary output of medical education programmes. It is important for institutions to identify systematically the types of medical activities in which their former students are involved in order to determine the effectiveness of the curriculum, assessing academic standards and reviewing admissions policies. Information was obtained from a survey of men and women graduates from three of the early graduation classes of King Abdulaziz University College of Medicine in Saudi Arabia about postgraduate medical training, certification, practice patterns, and other curriculum issues. Information collected from 151 graduates (90%) indicated that 96% were practising medicine in a variety of medical specialties and subspecialties. Six were not practising at the time of the study. Significant differences were found in the specialties being practised when men and women were compared. Men tended to practise in medicine, surgery, dermatology, urology, ENT, ophthalmology and orthopaedics, while women concentrated in obstetrics and gynaecology and paediatrics. Certification beyond medical school was earned by 49% with no significant difference being found comparing men to women. Men earned the majority of their postgraduate certifications outside Saudi Arabia while most women earned theirs in Saudi Arabia. Graduates indicated that departments in the basic sciences were least helpful in preparing them as doctors, while selected clinical departments were most helpful. It was concluded from the study that the curriculum goals of the College of Medicine, namely a curriculum of international standards producing graduates to take leadership roles in both teaching and medical practice, were realized in part by the graduates surveyed.

Comparison of glycosylated fibrinogen, albumin, and haemoglobin as indices of blood glucose control in diabetic patients.

The value of glycosylated fibrinogen as an index of short-term diabetic control was compared with indices of long-term (glycosylated haemoglobin) and intermediate-term (glycosylated albumin) diabetic control, respectively. In this study, percentages of these glycosylated proteins and fasting plasma glucose concentration were determined in 95 healthy non-diabetic subjects and 48 diabetic patients (22 well-controlled and 26 poorly-controlled) after an overnight fast. The differences in the percentages of glycosylated fibrinogen, haemoglobin, and albumin between non-diabetic subjects (4.7, 6.4, and 2.0), well-controlled diabetic patients (6.9, 9.5 and 2.9), and poorly-controlled diabetic patients (11.3, 15.8, and 5.1) were statistically significant (p less than 0.05). The percent glycosylated fibrinogen exhibited significant association with severity of hyperglycaemia when diabetic patients were divided by 2, 4, and 6 standard deviations above the mean of fasting plasma glucose of non-diabetic subjects. There were significant correlations between glycosylated fibrinogen and fasting plasma glucose (r = 0.83, p less than 0.001), glycosylated haemoglobin (r = 0.94, p less than 0.001) and glycosylated albumin (r = 0.92, p less than 0.001) for all subjects studied. In ten newly diagnosed diabetic patients after 6 days of treatment, only the decrease in glycosylated fibrinogen (33.4%) was significant (p less than 0.05), but not that of glycosylated haemoglobin (4.8%) or albumin (8.0%). It is suggested that glycosylated fibrinogen provides the clinician with earlier objective evidence of the metabolic response to therapeutic intervention, and might be regarded as a short-term (2-3 days) index of blood glucose control.

Prevalence of diabetes mellitus in rural Saudi Arabia.

Several studies have clearly shown the impact of modernization on the prevalence of diabetes mellitus in susceptible communities. Saudi Arabia has faced a rapid development program over the last two decades. In a recent study, we found a high prevalence of diabetes mellitus in urban Saudi Arabia. A total of 5222 rural subjects of both sexes were involved in a study of the prevalence of diabetes mellitus in the western region of Saudi Arabia. Random capillary blood glucose, body weight and height, and income were recorded. The results showed an overall prevalence of 4.3%. There was a rise of prevalence with age and higher-income groups. Prevalence also differed with sex. The overall prevalence in women (5.9%) was twice that for men (2.9%; P less than .001). Obesity occurred in 41.2% of our diabetic subjects compared to 29.3% in nondiabetic subjects (P less than .001). Multiple logistic regression analysis with body mass index (BMI) as the dependent variable showed that sex and income status were significant factors (P less than .0001 and P less than .04, respectively). When blood glucose was fixed as the dependent variable, the analysis showed that age, income, and BMI were significant factors (P less than .004, P less than .0001, and P less than .045, respectively).

Evaluation of the fluorescence polarization immunoassay for quantitation of digoxin in serum.

Digoxin in serum was measured by fluorescence polarization immunoassay (FPIA) and by radioimmunoassay (RIA). Intraday precision of the FPIA method determined by replicate analysis of three controls (low, medium, and high) gave coefficients of variation of 5.41, 2.67, and 2.37%, respectively. The interday coefficients of variation were 5.71, 4.55, and 1.93% for the low, medium, and high controls, respectively. The mean recovery for three spiked controls was 98%. Quantitative results obtained by FPIA on serum samples from patients receiving digoxin were compared with the results obtained by RIA. The correlation coefficient was 0.989. The stability of the standard curve in FPIA was evaluated by recalibrating the instrument at two intervals, 21 days apart, and superimposing the standard curve. No significant changes were found in polarization values.