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Journal Article 2009; 30(3): 352-356 PubMed PMID: 19855358 Citation  Keywords:  Acetic Acid:toxicity, Analgesia, Analysis of Variance, Animals, Anti-Inflammatory Agents, Non-Steroidal:pharmacology, Celecoxib, Chromatography, High Pressure Liquid, Dose-Response Relationship, Drug, Drug Synergism, Expectorants:administration & dosage, .   

OBJECTIVES: Previously, we found that guaifenesin enhances analgesia induced by paracetamol. The aim of the present study was to determine whether guaifenesin is able to also increase analgesic activity in the non-steroid anti-inflammatory drugs ibuprofen, nimesulide and celecoxib. In addition we investigated the influence of guaifenesin on plasma levels of nimesulide.

METHODS: A model of visceral pain consisting of intraperitoneal injection of acetic acid (writhing test) was used. Levels of nimesulide in plasma were measured by HPLC. All drugs were given orally and tested in mice.

RESULTS: Guaifenesin alone did not produce any antinociceptive effect. Simultaneous administration of guaifenesin (200 mg/kg) and subanalgesic doses of ibuprofen (10 and 30 mg/kg), nimesulide (10 and 20 mg/kg) or celecoxib (1 and 5 mg/kg) resulted in a significant antinociceptive effects. The plasma levels of nimesulide were significantly higher in combination with guaifenesin at 30, 60 and 90 min after oral administration in comparison to nimesulide monotherapy.

CONCLUSION: The present results suggest that guaifenesin might enhance the analgesic activity of various non-steroidal anti-inflammatory drugs....

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Journal Article 2009; 30(3): 343-351 PubMed PMID: 19855357 Citation  Keywords:  Adult, Age of Onset, Analysis of Variance, Body Height:genetics, Body Mass Index, Chi-Square Distribution, Female, Genetic Predisposition to Disease, Genotype, Haplotypes:genetics, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide:genetics, Psych.   

OBJECTIVES: The 102T/C single nucleotide polymorphism (SNP) in the 5-hydroxytryptamine receptor 2A (HTR2A) gene has been reported to be associated with schizophrenia. However, SNPs of the HTR2A gene other than the 102T/C have attracted only limited studies in relation to schizophrenia, and also on the whole SNPs of the HTR2A gene have been little studied in relation to clinical parameters in patients. Therefore, the aim of this study was to evaluate the impact of main functionally characterized SNPs of the HTR2A gene on both the schizophrenia and clinical parameters.

METHODS: Ninety-four patients with schizophrenia and 57 control subjects were genotyped for the -1438A/G, -783A/G, 102T/C and His452Tyr SNPs of the HTR2A gene. The four SNPs were then investigated in relation to the schizophrenia and clinical parameters.

RESULTS: No differences were found in genotype-, allele- or haplotype frequencies between schizophrenia patients and control subjects. However, the 452Tyr variant of the His452Tyr polymorphism occurred more often in patients with a family history of schizophrenia compared with patients without heredity (p=0.028). The 452Tyr variant was also more common in female patients with paranoid schizophrenia than in those with non-paranoid schizophrenia (p=0.018). Moreover, the male patients carrying the A/A or T/T genotypes of the -1438A/G and 102T/C polymorphisms were shorter than those carrying the G/A or C/T genotypes (p=0.007; p=0.006).

CONCLUSION: The present findings bring further support to the view that the -1438A/G, 102T/C and His452Tyr polymorphisms of the HTR2A gene are connected with a constitutive cellular change that causes susceptibility to schizophrenia....

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Journal Article 2009; 30(3): 335-342 PubMed PMID: 19855356 Citation  Keywords:  Analysis of Variance, Animals, Behavior, Animal:drug effects, Bornanes:pharmacology, Dose-Response Relationship, Drug, Grooming:drug effects, Hormone Antagonists:pharmacology, Male, Motor Activity:drug effects, Oxytocics:administration & dosage, Oxytocin:.   

OBJECTIVES: Oxytocin (OXY) in addition to peripheral actions has many central regulatory functions which can be studied on animal models. In the present study we examined in rats, which behavioral actions of OXY and long-acting carba-analog of OXY carbetocin (CBT) in the open-field can be inhibited by OXY-receptor antagonists. Our interest focused on the behavioral patterns considered indicative of anxiety-related behavior. To determine what is the participation of OXY receptor on OXY and CBT induced behavioral changes, we used two peptide and one nonpeptide OXY antagonists differing in selectivity for OXY receptor.

METHODS: OXY, CBT as well as OXY antagonists were injected intraperitoneally, and spontaneous behavior (horizontal and vertical activity, grooming) of Wistar rats was observed in the circular open-field arena 60 min after application of drugs; in some experiments testing was performed without treatment few days after drug administration.

RESULTS: OXY at the dose 0.05 mg/kg increased locomotion indicating anxiety attenuation, but 1.0 mg/kg reduced both locomotion and rearing. CBT in the dose range 0.1-3.0 mg/kg either did not change or increased horizontal activity. The increase in exploration after both peptides persisted for several days. A marked difference in the behavioral effects of the two peptides was grooming enhancement induced by OXY compared with the absence of this effect after CBT. The increase of the activity induced by OXY and CBT indicating anxiolytic-like action was blocked by OXY antagonists. However, the reduction of exploration induced by 1.0 mg dose of OXY was only partially reversed. The OXY induced enhanced grooming was completely antagonized by all used antagonists.

CONCLUSIONS: Behavioral effects of OXY and its antagonists after their i.p. application indicate that they penetrate blood brain barrier. The diversity in potency of OXY antagonists to inhibit grooming and other behaviors induced by OXY suggests that receptors participating in these behaviors may differ in brain localization, receptor conformation and/or in the utilized signaling pathways....

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Clinical Trial 2009; 30(3): 331-334 PubMed PMID: 19855355 Citation  Keywords:  Adult, Choline:immunology, Humans, Immunologic Factors:immunology, Lymphocyte Activation, Middle Aged, Multiple Sclerosis:diagnosis, Myelin Basic Protein:immunology, Peptide Fragments:immunology, Severity of Illness Index, Treatment Outcome,.   

: The efficacy of intravenous choline citrate infusions was investigated in 34 patients with multiple sclerosis (MS) by clinical evaluation and by monitoring of lymphocyte proliferation in vitro against fragments of myelin basic protein (MOG-35-55, MBP15-31, PLP 39-15) over a period of 12 weeks. Patients have been diagnosed with MS at least one year before entering the study and suffered from mild relapsing/remitting course to long-term chronic progressive disease. Twenty one patients exhibited positive lymphocyte proliferation to myelin fragments prior to treatment and were therefore selected for further studies. Choline citrate was administered with a dosage of 1200mg/ 2x week for a period of 3 months. This treatment resulted in a significant decrease of lymphocyte proliferation to neural fragments (MOG- 35-55, MBP15-31) in lymphocyte transformation test (LTT). There was no significant SI change of PLP Peptide (PLP 39-15) LTT found after treatment with choline citrate. During the 3 mo observation period, patients remained stable and no side-effects of the treatment were observed. In addition, some patients reported long-lasting improvement (less paresthesia and increase of muscle strength in lower extremities) which was demonstrated up to 3 years later. In one spectacular case a commercial pilot was able to return to duty again after treatment. This pilot was allowed back in to his position as a commercial flying cockpit member and is on duty for more than 4 yrs now....

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Case Reports 2009; 30(3): 327-330 PubMed PMID: 19855354 Citation  Keywords:  Adult, Affect:drug effects, Alcoholism:complications, Feeding and Eating Disorders:complications, Female, Humans, Naltrexone:therapeutic use, Narcotic Antagonists:therapeutic use, Self-Assessment,.   

: According to a recent literature review on the opioid mechanism in eating disorders, we found that there is increasing reason to re-examine the treatment potential of naltrexone. The endogenous opioid system belongs to the important modulators of food intake. The eating disorders share many traits with substance dependence models. We present two case histories of time-limited naltrexone therapy to show that, in clinical practice, individualized indication may contribute to short-term improvement and to prediction of a different long-term treatment outcome....

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Case Reports 2009; 30(3): 322-326 PubMed PMID: 19855353 Citation  Keywords:  Acromegaly:diagnosis, Congenital Hypothyroidism:diagnosis, Diagnosis, Differential, Humans, Male, Middle Aged, Thyroid Dysgenesis:diagnosis,.   

: Since introduction of population-based neonatal screening for congenital hypothyroidism (CH), cases of long-term untreated inborn hypothyreosis have become very rare whereas its clinical symptoms are currently not well known. We report a patient with CH due to an ectopic thyroid. The presented case is exceptional due to both advanced age of diagnosis and unusual clinical presentation, as the anomaly was detected during evaluation of suspected acromegaly at the age of 62. This report indicates that there is still necessity of considering, in spite of its rarity, congenital form in differential diagnosis of hypothyroidism....

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Case Reports 2009; 30(3): 312-321 PubMed PMID: 19855352 Citation  Keywords:  Aged, Antineoplastic Agents, Alkylating:therapeutic use, Antineoplastic Combined Chemotherapy Protocols:therapeutic use, Carcinoma:drug therapy, Cyclophosphamide:therapeutic use, Disease Progression, Drug Administration Schedule, Esophageal Neoplasms:drug.   

: The synergetic use of Somatostatin, Melatonin, Retinoids, Vitamins C, D3, and E, Calcium, sulphated Aminoglucosides, and minimum doses of cyclophosphamide in a 70-year old male patient with inoperable scarcely differentiated oesophageal carcinoma, has provided, from the beginning of treatment in 1995 to the present date, an excellent quality of life, as well as a cure with functional recovery. This paper discusses the rationale and molecular action mechanisms of the treatment which has a differentiating, apoptotic anti-proliferation effect, preserving and enhancing, unlike chemo- and/or radiotherapy, both the trophic and functional capacity of organs and tissues, and immunity and antiblastic homeostasis. This result confirms the efficacy of this biological multiple treatment (MDB); it is also in line with the positive results already published on the use of MDB in low-grade NHL (66) and in stage 3 or 4 lung carcinomas (53). The MDB, with no need for hospitalisation, no toxicity and without in the least reducing working activity, gradually and slowly reduced, and then eliminated the tumour formation. According to the author, reporting this case is useful in order to call for greater interest in the possibilities offered to oncology by the MDB biological and receptor treatment....

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Case Reports 2009; 30(3): 300-311 PubMed PMID: 19855351 Citation  Keywords:  Adult, Belgium, Cognitive Therapy, Diagnosis, Differential, Evidence-Based Medicine, Exercise Therapy, Fatigue Syndrome, Chronic:diagnosis, Female, Government, Humans, Inflammation:diagnosis, Outcome Assessment (Health Care),.   

: The World Health Organization acknowledges Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS) to be a medical illness. ME/CFS is characterized by disorders in the inflammatory and oxidative and nitrosative stress (IO&NS) pathways. In 2002, the Belgian government started with the development of CFS "Reference Centers", which implement a "psychosocial" model. The medical practices of these CFS Centers are defined by the Superior Health Council, e.g. treatment should be based upon Cognitive Behavioral Therapy (CBT) and Graded Exercise Therapy (GET); and biological assessments and treatments of ME/CFS should not be employed. Recently, the Belgian government has evaluated the outcome of the treatments at the CFS Centers. They concluded that a "rehabilitation therapy" with CBT/GET yielded no significant efficacy in the treatment of ME/CFS and that CBT/GET cannot be considered to be curative therapies. In case reports, we have shown that patients who were "treated" at those CFS centers with CBT/GET in fact suffered from IO&NS disorders, including intracellular inflammation, an increased translocation of gram-negative enterobacteria (leaky gut), autoimmune reactions and damage by O&NS. Considering the fact that these findings are exemplary for ME/CFS patients and that GET may even be harmful, it means that many patients are maltreated by the Belgian CFS Centers. Notwithstanding the above, the government and the CFS Centers not only continue this unethical and immoral policy, but also reinforce their use of CBT/GET in patients with ME/CFS treated at those Centers....

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