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Journal Article 2001; 22(1): 53-73 PubMed PMID: 11393163 Citation  Keywords:  Adrenal Glands:physiology, Animals, Biological Clocks, Blood Pressure:physiology, Chronobiology Disorders:physiopathology, Chronobiology Phenomena, Chronotherapy, Circadian Rhythm:physiology, Drug Administration Schedule, Genomics, Homeostasis, Humans, Pi.   

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Evaluation Studies 2009; 30(1): 32-38 PubMed PMID: 19300405 Citation  Keywords:  Adolescent, Adult, Anorexia Nervosa:diagnosis, Attitude to Health, Data Interpretation, Statistical, Diagnostic Techniques, Endocrine, Diagnostic Tests, Routine:statistics & numerical data, Female, Humans, Patient Admission, Patient Discharge:statistics &.   

OBJECTIVES: So far, no unequivocal answer has been provided to the question of how to treat girls with anorexia nervosa (AN). The goal of the study was evaluation of treatment results and search for prognostic factors, regarding the outcome of administered therapy in girls with AN.

PATIENTS AND METHODS: The analysis comprised eighty-seven (87) patients with diagnosis of AN. In the course of treatment, the patients received only a balanced and highly energetic diet. The effects of dietetic procedure were evaluated, comparing clinical data and routine laboratory test results (full blood cell count, serum concentrations of sodium, potassium, glucose, cholesterol, triglycerides, total calcium, phosphates, total protein and the urea) at the onset and on the last day of hospitalisation and also an analysis of clinical data in patients with regained menstrual cycles was performed. Also, on admission to hospital, serum concentrations of TSH, FT4, FT3, E2, T and cortisol were measured (the last hormone - three times - at 8:00, 17:00 and 24:00). Moreover, a stimulation test with GnRH was performed to assess LH and FSH release. A comparison was made between the clinical data, the results of routine laboratory tests and hormone concentrations, obtained at the beginning of the therapy in the group of cured girls (the girls with regained menses) and the group, in which the therapy did not bring complete elimination of the disease.

RESULTS: After hospitalisation, 75.9% of the patients with AN continued outpatient treatment. In all the patients, who adhered to proposed therapy, menstruation cycles returned within 1 to 12 months. It was found that in the group with positive treatment outcome, the patients were older, demonstrated higher BMI values at the beginning of the therapy, as well as shorter disease duration than those in the group of patients who refused further treatment. In the group of cured patients, estradiol concentrations were significantly higher and cortisol concentrations (at 17:00 and 24:00) were significantly lower, in comparison to the uncured group.

CONCLUSIONS: The findings suggest that body weight increase by proper diet application is the most important element of therapy in AN. Patient's age, disease duration, the degree of body weight loss and serum concentrations of estradiol and cortisol at 17:00 and 24:00 are the prognostic factors for the outcome of therapy in anorexia nervosa....

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Journal Article 2009; 30(1): 144-152 PubMed PMID: 19300402 Citation  Keywords:  Animals, Bradykinin:administration & dosage, Bradykinin Receptor Antagonists, Diabetes Mellitus, Experimental:chemically induced, Diabetic Neuropathies:chemically induced, Drug Evaluation, Preclinical, Enzyme Inhibitors:administration & dosage, Hyperalges.   

PURPOSE: The influence of an irreversible inhibitor of constitutive NO synthase (L-NOArg; 1.0 mg/kg ip), a relatively selective inhibitor of inducible NO synthase (L-NIL; 1.0 mg/kg ip) and a relatively specific inhibitor of neuronal NO synthase (7-NI; 0.1 mg/kg ip), on antihyperalgesic action of selective antagonists of B2 and B1 receptors: D-Arg-[Hyp3,Thi5,D-Tic7,Oic8] bradykinin (HOE 140; 70 nmol/kg ip) or des Arg10 HOE 140 (70 nmol/kg ip) respectively, in model of diabetic (streptozotocin-induced) and toxic (vincristine-induced) neuropathy was investigated.

METHODS: The changes in pain thresholds were determined using mechanical stimuli--the modification of the classic paw withdrawal test described by Randall-Selitto.

RESULTS: The results of this paper confirm that inhibition of bradykinin receptors and inducible NO synthase but not neuronal NO synthase activity reduces diabetic hyperalgesia. Pretreatment with L-NOArg and L-NIL but not 7-NI, significantly increases antihyperalgesic activity both HOE 140 and des Arg10 HOE 140. It was also shown that both products of inducible NO synthase and neuronal NO synthase activation as well as bradykinin are involved in hyperalgesia produced by vincristine. Moreover, L-NOArg and 7-NI but not L-NIL intensify antihyperalgesic activity of HOE 140 or des-Arg10HOE 140 in toxic neuropathy.

CONCLUSIONS: Results of these studies suggest that B1 and B2 receptors are engaged in transmission of nociceptive stimuli in both diabetic and toxic neuropathy. In streptozotocin-induced hyperalgesia, inducible NO synthase participates in pronociceptive activity of bradykinin, whereas in vincristine-induced hyperalgesia bradykinin seemed to activate neuronal NO synthase pathway. Therefore, concomitant administration of small doses of bradykinin receptor antagonists and NO synthase inhibitors can be effective in alleviation of neuropathic pain, even in hospital care....

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Comparative Study 2009; 30(1): 79-84 PubMed PMID: 19300401 Citation  Keywords:  Aggression:physiology, Animals, Aspartic Acid:analysis, Behavior, Animal:physiology, Brain:metabolism, Excitatory Amino Acids:analysis, Glutamic Acid:analysis, Male, Mice, Mice, Inbred ICR, Microchemistry:methods, Microdialysis:methods, Models, Biological.   

OBJECTIVES: Some individually-housed male mice behave aggressively during encounters with strange males, while others are timid or sociable in the same situation. The objective of the present study was to examine concentrations of glutamate, aspartate, and GABA in the brain of aggressive, timid, and sociable mice.

METHODS: Random-bred albino mice were housed individually for three weeks and then classified in three groups (aggressive, timid, and sociable mice) according to their behavior during social interaction with non-aggressive group-housed male mice in a neutral cage. One week after categorization, by means of the social conflict test, levels of glutamate, aspartate, and GABA were measured by in vivo microdialysis of the medial prefrontal cortex (mPFC) of the isolated and group-housed mice.

RESULTS: Sociable mice had almost triple the levels of GABA in their mPFC than aggressive or timid mice. No significant differences in aspartate and glutamate levels were found in these three types of individually-housed mice. Forebrain chemistry of group-housed mice did not differ from that of individually-housed mice with the exception of levels of glutamate and GABA which were significantly lower in group-housed mice than in sociable individually-housed mice.

CONCLUSION: The present results suggest that GABA might play a role in sociable behavior. Results also corroborate other findings indicating that the GABAergic system represents an important molecular and neuronal substrate for the selective attenuation of anxiety and aggression....

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Journal Article 2009; 30(1): 85-90 PubMed PMID: 19300400 Citation  Keywords:  Adolescent, Adult, Female, Humans, Male, Middle Aged, Multiple Sclerosis:cerebrospinal fluid, Nerve Growth Factor:cerebrospinal fluid, Neuromyelitis Optica:cerebrospinal fluid, Research Design, Severity of Illness Index, Thyroid Hormones:cerebrospinal flu.   

OBJECTIVE: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the human central nervous system (CNS) and a major cause of neurological disability among adults in North America and Europe. Neuromyelitis optica (NMO) is a very severe disease of inflammatory demyelination located in the optic chiasm, nerves and the spinal cord. The aim of this study is to assess thyroid hormone (TH) and nerve growth factor (NGF) levels in cerebrospinal fluid (CSF) of MS, NMO patients and controls, and investigate whether there is any correlation between TH and NGF levels in the CSF.

PATIENTS AND METHODS: 38 relapsing-remitting multiple sclerosis (RRMS), 10 NMO and 19 controls were investigated whether there was any correlation between TH and NGF levels in the CSF.

RESULTS: MS and NMO patients exhibited significantly higher CSF NGF (respectively P<0.05, P<0.05), TT4 levels (P<0.001) and higher TT4/ rT3 ratio (respectively P<0.01, P<0.01) compared with the controls. Significant correlation was found between CSF NGF levels and CSF rT3 levels or TT4/ rT3 ratio in controls (respectively P<0.01, P<0.05). EDSS was significantly correlated with CSF rT3 levels and TT4/ rT3 ratio in MS patients (respectively P<0.05, P<0.001).

CONCLUSIONS: These results indicate that an abnormal thyroid hormone may exist within the brain in the patients with MS. CSF rT3 levels and TT4/ rT3 ratio could be regarded as useful markers of underlying disease activity....

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Controlled Clinical Trial 2009; 30(1): 39-45 PubMed PMID: 19300399 Citation  Keywords:  Age Factors, Aged, Aged, 80 and over, Alzheimer Disease:diagnosis, Anisotropy, Corpus Callosum:diagnostic imaging, Diffusion Magnetic Resonance Imaging:methods, Echo-Planar Imaging:methods, Female, Humans, Male, Middle Aged, Organ Size, Psychological Test.   

OBJECTIVE: The aim of the study was to assess structural changes in gray matter (GM) volume and fractional anisotropy (FA) in patients with Alzheimer's disease (AD) compared to control subjects using Voxel-Based Morphometry (VBM). Fractional anisotropy in the corpus callosum of both groups was also calculated using ROI analysis.

METHODS: Twenty-one patients and twenty-three control subjects underwent MRI examination using T1-weighted 3D MPRAGE sequence and diffusion spin-echo echo-planar imaging sequence in six directions. Structural MRI analyses for GM volume and FA were performed using an optimized VBM protocol implemented in SPM5. The influence of age and Mini-Mental State Examination (MMSE) was dealt with multiple regression analysis either for the whole group or for AD patients and controls separately.

RESULTS: Patients showed significant reduction of GM volume mainly in the temporal lobes. In AD patients, no correlation was observed between GM volume and age or MMSE. FA was reduced in AD patients mainly in frontal and temporal lobes. In both groups no correlation was found between FA and age or MMSE. Patients with AD showed a significant decrease in FA and an increase in mean diffusivity (p<0.0001) in the corpus callosum.

CONCLUSIONS: In patients with AD we observed a significant reduction in FA values and GM volume; however, no correlation with age and MMSE was proven for both FA and GM for AD patients. This finding supports the hypothesis that morphological changes in patients with AD are not a continuous aging related process but represent qualitative changes....

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Comparative Study 2009; 30(1): 46-50 PubMed PMID: 19300398 Citation  Keywords:  Amyloid beta-Peptides:blood, Animals, Brain:metabolism, Guinea Pigs, Kidney:metabolism, Male, Orchiectomy, Testosterone:metabolism, Time Factors,.   

OBJECTIVES: The association between low testosterone levels and Alzheimer's disease (AD) amyloid beta-peptide (Abeta) metabolism was investigated in brain and kidney of guinea pigs.

METHODS: The expression of Abeta peptide in the brain and kidney was assessed by using the immunohistochemistry method.

RESULTS: No expression of Abeta was seen in both groups of animals. This negative staining was found until the fourth week following castration. The formation of Abeta in guinea pigs is perhaps not a short duration process and may undergo different metabolic pathway compare to humans.

CONCLUSION: castration was not associated with the formation of Abeta in the brain and kidneys during a 1-month period and might require a longer period of time....

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Clinical Trial 2009; 30(1): 74-78 PubMed PMID: 19300394 Citation  Keywords:  Administration, Oral, Adult, Biological Availability, Calibration, Chemistry, Pharmaceutical:standards, Cross-Over Studies, Dose-Response Relationship, Drug, Humans, Hypoglycemic Agents:administration & dosage, Injections, Subcutaneous, Insulin:administra.   

OBJECTIVE: The purpose of this study is to investigate oral absorption of 1, 2 and 3 U/kg oral insulin five test products with different particle sizes in comparison with 0.1 U/kg subcutaneous reference formulation.

METHODS: Twenty five healthy volunteers participated in five studies using a two-phase, two-sequence crossover design with washout period of one day. Mean disposition kinetics was determined by non-compartmental analysis using Kinetica program. Absorption kinetics of insulin products were then determined using SIMCYP simulator utilizing ADAM model.

RESULTS & CONCLUSIONS: Dimensional analysis results showed the superiority of formula 4:2 U/kg oral dose with 57 nm particle size over other oral formulations when compared with subcutaneous route. Optimized intestinal permeability coefficients (x10(-4)) of insulin best test and reference formulations were 0.084 and 0.179 cm/sec respectively. Total fraction of insulin dose absorbed (Fa) for the test and reference products were 3.0% and 19% respectively. Subcutaneous product exhibited higher absorption rate and extent than oral insulin. Yet that was compensated by the increase in other factors such as Fa*, Peff* and oral dose, leading to similar insulin plasma levels and similar effect on glucose infusion rates. Oral insulin bioavailability was shown promising for the development of oral insulin product....

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