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Journal Article 2013; 34(7): 660-668 PubMed PMID: 24464005 Citation  Keywords:  Adult, Aged, Antineoplastic Combined Chemotherapy Protocols:administration & dosage, Breast Neoplasms:drug therapy, Cholecalciferol:administration & dosage, Cyclophosphamide:administration & dosage, Female, Follow-Up Studies, Humans, Melatonin:administrat.   

OBJECTIVE: The current strategies for the treatment of breast cancer are essentially based on surgery, preceded and/or followed by chemotherapy often supplemented by radiotherapy and/or the administration of hormonal therapy and monoclonal antibodies. Their combined use has made it possible to increase an overall survival but they are still penalized by adverse effects and toxicity. The marked anti-cancer effects of biological molecule such as somatostatin, melatonin, retinoid, vitamin D3 and prolactin inhibitors have been studied and documented for several decades. Their integrated and synergic action have been demonstrated, but only a few studies have as yet been carried out on their combined application in humans. The aim of the present investigation was to evaluate both the objective clinical response and toxicity of the biological multimodal treatment named Di Bella Method (DBM).

MATERIAL AND METHODS: The clinical data from a total of 20 women with a certified diagnosis of breast cancer,defined disease stage, and who independently decided to follow the DBM as first-line treatment, were retrospectively reviewed.

RESULTS: The mean age of the patients was 51 years (min 30; max 73). Twelve (12) patients (60%) presented an early stage disease, while the other 40% had a locally advanced/metastatic stage. An overall clinical benefit was achieved in 75% of cases, with 55% of complete response and 20% of partial response. For metastatic patients, the overall survival rate was 71%. The main toxicity effects included leukopenia, gastrointestinal phenomena and drowsiness.

CONCLUSIONS: The preliminary results of this report confirm the positive action of the biological treatment in terms of efficacy and survival, showing a more than favorable profile of tolerability....

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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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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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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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Case Reports 2013; 34(6): 508-513 PubMed PMID: 24378452 Citation  Keywords:  ADAM Proteins:genetics, ADAMTS13 Protein, Fatal Outcome, Female, Humans, Male, Platelet Aggregation:genetics, Pregnancy, Pregnancy Complications, Hematologic:genetics, Pregnancy Outcome, Purpura, Thrombotic Thrombocytopenic:genetics, Twins, Young Adult,.   

OBJECTIVE: The primary pathologic reason for thrombotic thrombocytopenic purpura (TTP) lies in the systemic formation of platelet aggregations in association with endothelial cells damage. Endothelial damage is a result of an abnormal synthesis and metabolism of unusually large von Willebrand Factor (ULvWF) multimers. In normal conditions vWF cleaving metalloprotease, known as ADAMTS-13 (A Disintegrin And Metalloproteinase with Thrombospondin type-1 motif, member 13) prevents the ULvWF entrance in the circulation. It already has been proven that thrombotic thrombocytopenic purpura is strongly correlated with severe congenital or acquired deficiency of ADAMTS-13. Congenital ADAMTS-13 deficiency is known as Upshaw-Schulman Syndrome and it accounts for only 2-4% of all TTP cases. It is conditioned by genetic variants of the ADAMTS-13 gene causing reduced ADAMTS-13 synthesis and shows an autosomal recessive type of inheritance.

CASE PRESENTATION: We present an interesting case of a 20 year old patient, primigravida, nulliparous, in 28th gestational week of twin pregnancy with undiagnosed Upshaw-Schulman Syndrome. The patient was transferred from the district hospital to the Tertiary Perinatal Care Center because of thrombocytopenia and suspicion of hemolytic-uremic syndrome. Genetic analysis performed 5 years after patient's death (before 2008 that kind of genetic analysis had not been available in Poland) showed a homozygotic mutation in the ADMTS13 gene (4143insA) which confirmed the diagnosis of Upshaw-Schulman Syndrome.

CONCLUSIONS: 1. TTP, especially hereditary Upshaw-Schulman Syndrome, is extremely rare and complicates the course of pregnancy. It is usually very sudden and dramatic; 2. Differential diagnosis of this disease is difficult and treatment strategy very burdensome for the patient. For this reason, diagnosis of micro-angiopathic disorders need to be simultaneously based on both clinical symptoms and laboratory findings; 3. Genetic diagnosis that confirms exact recognition of Upshaw-Schulman Syndrome is not commonly available; 4. The described case was a huge diagnostic challenge, and actually the final diagnosis was published until five years after the patient's death. Before 2008, that type of genetic analysis had not been available in Poland; 5. Despite the enormous progress in medical knowledge and experience, the exact diagnosis of TTP, including Upshaw-Schulman Syndrome, of this condition remains very difficult....

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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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Journal Article 2013; 34(6): 543-548 PubMed PMID: 24378445 Citation  Keywords:  Age Factors, Animals, Animals, Newborn, Body Weight:physiology, Energy Metabolism:physiology, Estrogen Receptor alpha:blood, Female, Food Deprivation:physiology, Hypothalamus:growth & development, Leptin:blood, Pregnancy, RNA, Messenger:metabolism, Rats,.   

OBJECTIVE: Estrogen plays an important role in feeding and energy balance, and the critical role of estrogen in the control of appetite and energy balance is mediated by hypothalamic estrogen receptor (ER) alpha. In undernourished rodents, hypothalamic ER alpha mRNA expression are decreased. Responses of some hypothalamic factors to negative energy balance develop during the early neonatal period.

DESIGN: In this study, we examined the developmental changes of fasting-induced alterations in hypothalamic ER alpha mRNA expression in female rats.

RESULTS: ER alpha mRNA expression was reduced after a 12-h or 24-h fast at postnatal days 15 and 25, but not at day 5. Serum estradiol levels in postnatal day 25 rats were not changed by fasting. Although serum leptin levels were suppressed by fasting at all ages, hypothalamic ER alpha mRNA expression at postnatal day 25 was not changed by leptin administration after a 24-h fast.

CONCLUSIONS: These data show that the sensitivity of hypothalamic ER alpha to negative energy balance may not be established in the early neonatal period, and that it develops by postnatal day 15. Decreased leptin levels might not be involved in the alterations of hypothalamic ER alpha mRNA expression in the undernourished condition....

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