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Journal Article 2013; 34(6): 523-528 PubMed PMID: 24378460 Citation  Keywords:  Adult, Aged, Antineoplastic Combined Chemotherapy Protocols:administration & dosage, Cholecalciferol:administration & dosage, Cyclophosphamide:administration & dosage, Dopamine Agonists:administration & dosage, Humans, Male, Melatonin:administration & dos.   

OBJECTIVE: To evaluate the objective clinical response and the safety of the combined administration of somatostatin, melatonin, retinoids, vitamin D3, dopamine subtype 2 receptor (D2R) agonists and low doses of cyclophosphamide, associated with androgen ablation, in patients with a histological diagnosis of prostate adenocarcinoma (Pac).

MATERIALS AND METHODS: The clinical data of 30 patients with non-invasive and metastatic prostate cancer, who attended our institution over a period of more than 5 years, were retrospectively reviewed.

RESULTS: 16 patients satisfied the evaluation criteria. Median age: 64 years. Disease stages: 8 patients (50%) were in Stage II. For advanced stages (Stage IV), secondary lesions were located in the bones and lymph nodes. Taken together, an overall objective response (OR) [Complete response (CR) + Partial Response (PR)] was achieved in 69% of the patients, with 88% of objective clinical benefit [CR+PR+SD]. For local Prostate Cancer group, an OR was achieved in 87.5% of patients (7 cases; 53-98; 95% CI), with CR in 62.5% (5 cases, 31-86; 95% CI). In metastatic disease, the OR was 50% (4 cases; 21-78; 95% CI), with a 20% of CR (2 cases; 7-59; 95% CI) and 75% of clinical benefit.

CONCLUSIONS: This preliminary study shows that patients with early and advanced forms of prostate cancer, not previously treated by surgery and/or chemo-radiotherapy, can achieve a more than positive clinical benefit with the protocol foreseen by the Di Bella Method. Further clinical investigations are strongly recommended....

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Journal Article 2013; 34(6): 518-522 PubMed PMID: 24378459 Citation  Keywords:  Adolescent, Blood Pressure:drug effects, Dose-Response Relationship, Drug, Female, Humans, Hypertension:chemically induced, Infant, Male, Vitamin D:administration & dosage, Vitamin D Deficiency:drug therapy, Vitamins:administration & dosage,.   

OBJECTIVE: The broad spectrum of extraosseal functions of vitamin D has recently been investigated. Although majority of recent studies have documented its hypotensive effect, some older studies warrant the risk of development the juvenile hypertension namely after pulse-fortified D vitamin supplementation during infancy. The aim of this study was to compare of the blood pressure in 13 year old groups of adolescents to the mode of D vitamin supplementation during their infancy.

METHODS: Study group represent 1138 thirteen year old adolescents in complex health care of 21 primary care pediatricians (PCPs). This group was divided into three subgroups according their mode of D vitamin supplementation in infancy. 100 children were given the continuous daily supplementation of AD vitamin 200-400 IU /day - " regular subgroup 0", 933 children were given by bolus doses of D vitamin forte 450 000 IU every three months during first year of life - "fortified subgroup 2", and 105 children given by bolus doses of D vitamin during winter, and continuous daily AD drops during summer - " mixed subgroup 1". D vitamin supplementation was done approximately 13 years before blood pressure study.

RESULTS: The mean systolic blood pressure was 110 mmHg, and mean diastolic one was 70 mmHg in all subgroups, regardless the mode of vitamin D supplementation. There were no statistic differences among subgroups, between girls/ boys, blood pressure levels were in normal limit. Although calculated daily doses of D2 vitamin during infancy exceeded RDA (200-400 IU) four to ten time, no difference in morbidity was found, concerning various chronic diseases (allergy, cardiovascular, renal, etc.). These results are in full accordance to recent knowledge of higher requirement and safety limit during vitamin D application.

CONCLUSION: The mode of D vitamin prophylaxis during infancy (pulse or daily application) has no influence to blood pressure level in early adolescence. No adverse effects have been found despite that the calculated daily dose was exceeded from three to ten times the recommended daily allowance....

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Journal Article 2013; 34(6): 539-542 PubMed PMID: 24378457 Citation  Keywords:  Adult, Aged, Aged, 80 and over, Choroid Neoplasms:diagnosis, Diagnosis, Differential, Female, Follow-Up Studies, Humans, Male, Melanoma:diagnosis, Middle Aged, Nevus, Pigmented:diagnosis, Optic Disk:pathology, Retinal Pigment Epithelium:pathology, Tomogra.   

OBJECTIVE: To assess the utility of the optical coherence tomography (OCT) in diagnosing, differentiating and monitoring of choroidal nevi situated in the posterior pole and optic disc area.

MATERIAL AND METHOD: 116 consecutive patients (65 women, 51 men) aged 27-95 years, with choroidal nevus were included to the research. Routine ophthalmoscopic evaluation and OCT using the Zeiss Stratus OCT as well as fundus photography were performed in each patient. The OCT was used to assess the structure of the retina overlying the choroidal nevus, the retinal pigment epithelium (RPE) - choriocapillaris complex, as well as the anterior portion of the choroidal lesion. In 31 patients due to suspected malignant melanoma fluorescein angiography and ultrasound were additionally performed. Follow-up OCT was done after 12 months in 51 out of 85 patients with characteristics of choroidal nevi, and after 6 and 12 months in 27 patients with "suspicious" lesion.

RESULTS: The basal dimension of the lesion ranged from 0.5 mm to 12 mm (mean 2.75mm), mean thickness was 1.25 mm. The pigmented lesion did not affect visual acuity. In 85 patients the lesion was flat or slightly elevated, without secondary changes in the retina. In 31 patients additional changes in the retina were observed - most frequently subretinal fluid. Two patients were eventually diagnosed with malignant melanoma. The follow-up OCT did not show progression in neither patients without secondary changes nor those with risk factors of malignancy.

CONCLUSION: Optical coherence tomography enables detailed evaluation of the retina overlying the pigmented lesion. Secondary changes in the retina need additional exams and strict observation. OCT could be an additional tool in the evaluation of treatment of malignant melanoma....

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Controlled Clinical Trial 2013; 34(6): 559-565 PubMed PMID: 24378456 Citation  Keywords:  Adult, Aged, Cadmium:adverse effects, Chronic Disease, Dental Amalgam:adverse effects, Female, Fibromyalgia:etiology, Humans, Hypersensitivity:complications, Lead:adverse effects, Lymphocyte Activation:immunology, Mercury:adverse effects, Metals:adverse e.   

BACKGROUND: Fibromyalgia (FM) is a disease of unknown etiology. Inflammation could be one of the mechanisms behind this disease.

OBJECTIVES: We studied the frequency and clinical relevance of metal allergy in FM patients.

METHODS: Fifteen female FM patients were included in the study. Metal allergy was measured by a lymphocyte transformation test, MELISA®. Ten healthy age-matched women were used as controls for in vitro studies. Reduction of metal exposure in the FM patients was achieved by replacement of dental metal restorations and by the avoidance of known sources of metal exposure. Objective health assessment was performed 5 years after treatment. Subjective health assessment was established by a questionnaire, completed 2, 5 and in some cases 10 years after the start of the study. Follow-up MELISA was also performed.

RESULTS: All FM patients tested positive to at least one of the metals tested. The most frequent reactions were to nickel, followed by inorganic mercury, cadmium and lead. Some healthy controls responded to inorganic mercury in vitro but most of the tests were negative. Objective examination 5 years later showed that half of the patients no longer fulfilled the FM diagnosis, 20% had improved and the remaining 30% still had FM. All patients reported subjective health improvement. This correlated with the normalisation of metal-specific responses in vitro.

CONCLUSION: Metal allergy is frequent in FM patients. The reduction of metal exposure resulted in improved health in the majority of metal-sensitized patients. This suggests that metal-induced inflammation might be an important risk factor in a subset of patients with FM....

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Case Reports 2013; 34(6): 504-507 PubMed PMID: 24378455 Citation  Keywords:  Aged, Aluminum:blood, Alzheimer Disease:drug therapy, Antioxidants:therapeutic use, Ascorbic Acid:therapeutic use, Chelation Therapy:methods, Deferoxamine:therapeutic use, Epilepsy:drug therapy, Fatal Outcome, Female, Humans, Iron:blood, Siderophores:ther.   

: In this case presentation, a woman with high serum levels of aluminum was treated with chelation therapy with deferoxamine and ascorbic acid. This patient was initially bedridden and the clinical situation was complicated by epileptic seizures. After the chelation therapy, the clinical condition was ameliorated and the therapy continued without the correlation to aluminum serum levels. The role of metals in neurodegenerative disorders and the correlation between iron metabolism and amyloid beta peptide are described. This case suggests chelation therapy could represent a promising therapeutic option for this dramatic disease....

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Journal Article 2013; 34(6): 529-538 PubMed PMID: 24378454 Citation  Keywords:  Animals, Antibodies, Monoclonal:pharmacology, Apoptosis:drug effects, Boron Compounds:pharmacology, Cells, Cultured, Cerebellum:cytology, Cytokine Receptor gp130:antagonists & inhibitors, Dantrolene:pharmacology, Drug Interactions, Excitatory Amino Acid A.   

OBJECTIVE: To reveal the involvement of inositol 1,4,5-trisphosphate receptors (IP3R) and ryanodine receptors (RyR) in IL-6 prevention from neuronal apoptosis and necrosis induced by N-methyl-D-aspartate (NMDA).

METHODS: Cerebellar granule neurons (CGNs) from 8-day-old rats were exposed to IL-6 for 8 days and then stimulated with NMDA for 30 min. The 2-aminoethoxydiphenyl borate (2-APB) and dantrolene (DAN) were used to antagonize IP3R and RyR, respectively. Anti-gp130 monoclonal antibody (mAb) was employed to neutralize gp130, a 130-kDa signal-transducing β-subunit of IL-6 receptor complex. Neuronal apoptosis and necrosis were determined by TUNEL, fluorometric caspase-3 enzyme activity, annexin V-FITC/PI staining and ELISA. Western blot and real-time PCR measured IP3R1 and RyR2 expression, respectively.

RESULTS: IL-6 prevented the elevation of TUNEL-positive cells and caspase-3 expression and activity, and also suppressed the increase in annexin V-FITC/PI-positive cells and DNA- and histone-associated nucleosomes in cultured CGNs evoked by NMDA. These anti-apoptotic and anti-necrotic effects of IL-6 were larger on DAN-treated cells than on 2-APB-exposed neurons, since 2-APB treatment alone significantly inhibited the neuronal apoptosis and necrosis but DAN exposure alone did not alter the apoptosis and necrosis induced by NMDA. In support of these results, IL-6 downregulated IP3R1 but did not affect RyR2 expression. All these IL-6 effects were blocked by anti-gp130 mAb.

CONCLUSION: IL-6 prevention from NMDA-triggered Ca2+-induced Ca2+ release-mediated apoptosis and necrosis in CGNs depends on the inhibition of IP3R channel opening and expression rather than on RyR activity. IL-6 receptor-coupled gp130 signaling mediates this neuroprotection of IL-6 resistance to neuronal apoptosis and necrosis....

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Journal Article 2013; 34(6): 573-578 PubMed PMID: 24378453 Citation  Keywords:  Animals, Biocompatible Materials:chemistry, Cattle, Dendrimers:chemistry, Drug Interactions, Hypoglycemic Agents:chemistry, Insulin:chemistry, Protein Binding, Protein Conformation, Spectrometry, Fluorescence, Tyrosine:chemistry,.   

OBJECTIVE: In this study the mechanism of interactions between polyamidoamine (PAMAM) dendrimers and bovine insulin was examined. The insulin is a 51 amino acid peptide-hormone involved in the homeostasis of blood glucose levels. This molecule consists of two chains - A and B - linked by two disulphide bridges. As insulin contains four tyrosine residues it was possible to evaluate dendrimers effect on protein conformation by measuring changes in the fluorescence spectra of insulin after addition of dendrimers or classical quenchers.

METHODS: PAMAM dendrimers are based on ethylenediamine core and branched units which are built from methyl acrylate and ethylenediamine. PAMAM dendrimers with different surface groups (-COOH, -NH2, -OH) were used. Their size is comparable to insulin.

RESULTS: The experiments show that interactions exist between PAMAM dendrimers and insulin. It was found that these interactions depend on a kind of dendrimer surface groups.

CONCLUSIONS: It is very likely that interactions are of electrostatic nature and cause insulin conformational changes....

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Clinical Trial 2013; 34(6): 566-572 PubMed PMID: 24378447 Citation  Keywords:  Adolescent, Adult, Animals, Contraceptives, Oral:administration & dosage, Dogs, Facial Pain:drug therapy, Female, Follow-Up Studies, Humans, Menstrual Cycle, Middle Aged, Risk Factors, Temporomandibular Joint:pathology, Temporomandibular Joint Disorders:d.   

OBJECTIVE: The prevalence of signs and symptoms of temporomandibular disorders (TMD) is the highest among women of reproductive age. Estrogens are the major contributor to the regulation of bone growth and development. They also influence peripheral and central mechanism of pain. The aim of this study was to evaluate the efficacy of conservative treatment of temporomandibular joint (TMJ) internal derangements in regular cycling women with and without use of oral contraceptives (OCs).

MATERIAL & METHODS: The study included 229 women with TMJ disk displacement with and without reduction (DDwR and DDw/oR). The study group consisted of 191 normally cycling women and 38 women using combined OCs (COCs). The conservative TMD treatment was applied and its efficacy was rated during check-up visits.

RESULTS: The decreased odds of obtaining any or sufficient improvement during control visits were observed in women treated for DDwR and taking COCs for less than 3 years (p=0.01). There was a 2.7-fold higher risk for the failure of treatment in women taking COCs for less than 3 years during control visits in both diagnoses, DDwR or DDw/oR (p=0.082). There was investigated an increase in the risk for the lack of sufficient post-treatment improvement in diagnosed DDwR or DDw/oR in women with co-occurrence general osteoarticular lesions (p=0.07, p=0.04).

CONCLUSIONS: A worse TMJ internal derangements treatment efficacy was observed in women taking COCs for rather short time (less than 3 years) and in women with disorders in the osteoarticular system, what indicates modification of therapeutic procedures in that groups of patients....

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