Selective Imidazoline Receptor Agonists: redefining the role of centrally acting agents in management of hypertension

Hypertension, often referred to as ‘The silent killer’, is christened so, as it is seldom preceded by any warning signs or symptoms. With the new ACC/AHA guidelines lowering the Blood Pressure (BP) threshold values, it has resulted in a 140% relative increase in the hypertension prevalence in India, which is 3 times higher than that of in United States. Imidazoline receptor agonists control BP effectively with minimal adverse effects of sedation and mental depression that are usually associated with centrally acting antihypertensives. While having a low affinity to the α2-adrenergic receptors, these new generation centrally acting antihypertensive agents are highly selective for imidazoline receptor. Moxonidine, a second-generation centrally acting antihypertensive drug having selective agonist activity on imidazoline I1 receptors and minor activity on imidazoline α2 adrenoceptors, reduces the activity of Sympathetic Nervous System (SNS) by activating I1 imidazoline receptors in Rostral Ventrolateral Medulla (RVLM). Studies of moxonidine have shown equal effectiveness in lowering BP like other well-established antihypertensive drugs such as nifedipine, atenolol or angiotensin-converting enzyme inhibitors, with minimal adverse events. At doses of 0.2-0.6 mg, moxonidine induces satisfactory BP reduction in patients with mild-to-moderate essential hypertension. In patients with mild-to-moderate hypertension, moxonidine (0.2-0.4 mg o.d.) significantly decreased Systolic Blood Pressure/Diastolic Blood Pressure (SBP/DBP), respectively, by 19.5/11.6 mmHg. In obese, non-controlled hypertensive patients, there is a 14% and 13.5% reduction in the mean SBP and DBP, respectively, from the baseline value after moxonidine treatment and during the follow-up with an additional reduction in body weight, plasma leptin levels and Body Mass Index (BMI) (p<0.01). Thus, moxonidine could be considered as a therapeutic option in obese patients with metabolic syndrome.

Malignant melanoma of the mandibular gingiva: A rare occurrence.

Primary mucosal malignant melanoma of the oral cavity is a rare tumor. It accounts for only 0.2-8% of all malignant melanomas. This malignancy commonly affects male subjects and is more frequently seen on the hard palate and maxillary gingiva. The peak age for diagnosis of oral melanoma is between 55 and 65 years. A biopsy is required to establish a diagnosis. Ablative surgery with tumor-free margins remains the treatment of choice. It has a much poorer prognosis than its counterpart on the skin. Here, we present a case of malignant melanoma of the mandibular lingual gingiva in a 55-year-old male patient. Immunohistochemistry and special stains were conducted for confirmatory diagnosis.

A clinical decision support system using multilayer perceptron neural network to assess well being in diabetes.

Background : Diabetes mellitus is an increasingly common life-style disorder whose management outcomes are measured in symptomatic, biochemical as well as psychological areas. Well being as an outcome of treatment is being increasingly recognized as a crucial component of treatment. There is little published literature on psychosocial outcomes and the factors influencing them. Therefore we have developed a neural network system which is trained to predict the well being in diabetes, using data generated in real life. Material and Methods : We developed a Multi Layer Perceptron Neural Network model, which had been trained by back propagation algorithm. Data was used from a cohort of 241 individuals with diabetes. We used age, gender, weight, fasting plasma glucose as a set of inputs and predicted measures of well - being (depression, anxiety, energy and positive well-being). Results : It was observed that female patients report significantly higher levels of depression than their male counter parts. Some slight high or no significant differences are observed between males and female patients with regard to the number of persons with whom they share their anxieties and fears regarding diabetes. There is not much difference has been observed in energy levels of both males and females. Also, Males have higher pwb value when compared with the female counterparts. Also, this may be due to women tend to react more emotionally to disease and hence experience more difficulty in coping with it. The present sample of women being predominantly house wives may be worrying more about their health and its problems. Also, it is observed that, gender differences are significant with regard to total general well-being. With five inputs (age, sex, weight, fasting plasma glucose, bias), four outputs are four (depression, anxiety, energy and positive well-being) the momentum rate was 0.9, the learning rate 0.7, using a sample of 50. the maximum individual error is 0.001 when the number of iterations were 500, number of hidden layers is 1 and the number of units in the hidden layer are 6, the normalized system error was 470.57. With input samples of 100, 150 and 200, keeping the other variables constant, the normalized system error was 419.61, 359.67 and 332.32 respectively. Similar values are found for the normalized system error when the number of units in the hidden layer have been increased to 7, 8 and 9 respectively. With two hidden layers, and with each hidden layer containing 6,7,8,9,10,11 units for the samples 50,100,150, and 200, the same values of normalized system error was found.. Women having weight between 40kgs and 85kgs had higher levels of depression than men who had weight between 39kgs and 102kgs. Conclusion : We have developed a prototype neural network model to predict the psychosocial well-being in diabetes, when biological or biographical variables are given as inputs. When greater data was fed to the system, the normalized system error can be reduced. ©

Psychosocial aspects of women with polycystic ovary syndrome from south India.

BACKGROUND: Polycystic ovary syndrome (PCOS), though initially manifesting with reproductive and cosmetic symptoms is a harbinger of insulin resistance syndrome. It is associated with psychological distress in both management as well as in its etiology. There are no Indian studies on psychological stress in women with PCOS. METHODS: Ninety nine women who presented with PCOS to the Endocrinology clinic were administered Goldberg's GHQ 28 (General Health Questionnaire) to assess psychological status, along with clinical, hormonal and ultrasound evaluation. RESULTS: Fifty four percent had a GHQ28 score >8. Among them 38% had a family size <4, 72% had obesity, 70% had hirsutism, 72% had a waist circumference >88 cm and 69% had a F/G score >4 . All these variables were statistically significant; p < 0.05 using Chi-square test. CONCLUSION: Women presenting with PCOS had increased psychological distress, which was related to smaller size of family, and more severe physical manifestations of the condition.

Psychiatric co-morbidity & diabetes.

Diabetes mellitus as well as psychiatric disorders are common. These may occur with one another and/or one may worsen the other. Psychological stress may follow screening for diabetes, as well as when diabetes is first identified. Acting through the hypothalamo-pituitary-adrenal axis, stress may initiate or worsen hyperglycaemia. Depression may be a risk factor for the development of diabetes; it also commonly occurs in subjects with diabetes. Identification and management are both important in preventing the disability. A variety of antipsychotic medications, especially the newer agents can induce weight gain, dyslipidaemia, insulin resistance and diabetes. Therefore in choosing a drug, one must consider the risk factors and screen for metabolic syndrome. Subjects with type 1 diabetes can have cognitive dysfunction, eating disorders and developmental disturbances. Physicians caring for people with diabetes must be trained to recognize and manage co-morbid psychiatric conditions that commonly occur. A biopsychosocial disease model for both conditions can leverage the social strengths and medical knowledge in developing countries.

Phylogenetic tree construction of butyrylcholinesterase sequences in life forms.

Butyrylcholinesterase is an enzyme with few known physiological functions. It is related to acetylcholine that was shown to be expressed in a variety of life forms. We performed a search using the human butyrylcholinesterase gene (HGNC:983;MIM:177400), and found the sequence in a broad spectrum including plants, bacteria and animals. Therefore butyrylcholinesterase appears to have evolved early in evolution, and to have been conserved.

Peroxisome proliferator-activated receptors as molecular targets for drug therapy.

Peroxisome proliferator-activated receptors (PPAR) are a family of nuclear receptors that regulate lipid and carbohydrate metabolism in response to extracellular fatty acids and their metabolites. They are crucial in the regulation of fat storage, besides having a potential role in insulin resistance syndrome. They have clinical relevance in understanding the cause and in development of drugs in common clinical conditions such as type 2 diabetes mellitus, cellular growth and neoplasia. Three types of receptors were identified: PPAR alpha, gamma and delta. Fibrate group of lipid lowering agents bind to the alpha isoform and glitazone group of insulin sensitizers to gamma isoform. Further advances can result in new drugs for atherosclerosis, malignancies and diabetes mellitus.

Impact of human genome project on medical practice.

The sequence of bases on all 23 pairs of human chromosomes has been nearly unravelled. Nearly 3.1 billion nucleotide bases were sequenced using the clone based approach of Human Genome Project Consortium and the shotgun approach of Celera. There appear to be about 30,000 genes, which are however more complex. Human genes seem to have been transferred over evolution from bacteria. Further progress is likely in identifying genes and their function, in development of DNA chips or arrays to identify genes, expanded field of protomics or the study of detailed structure and function of proteins. Pharmacogenomics is possible to develop designer drugs depending on the individuals genetic make-up. Projected drawbacks from availability of genetic data of individuals include loss of privacy, genetic determinism and the risk of high insurance premia, conflict about patenting and ownership.

Adenoid cystic carcinoma of the external auditory canal with pulmonary, renal and liver metastases.

We report a patient with adenoid cystic carcinoma of the external auditory canal with multiple pulmonary, liver and renal secondaries. She had a palpable left renal mass. The clinical course and treatment of this unusual neoplasm as reported in literature are briefly reviewed.