Diagnosis of pancreatitis is based on the determination of serum amylase and lipase levels. However, recent identification of specific leptin receptors in the pancreas suggests that this peptide may also play some roles in the modulation of pancreatic function. The objective of the present study was to investigate the relationship between serum leptin levels and pancreatitis. Thirty male Wistar rats were divided into 3 groups: the control group, acute pancreatitis group and chronic pancreatitis group. Pancreatitis was induced by injection of ethyl alcohol into the common biliary duct. A sham laparotomy was performed in the control group. Control and acute pancreatitis groups were sacrificed 24 hours later, and chronic pancreatitis group was sacrificed on postoperative day 7. Blood was taken by cardiac puncture for the determination of plasma leptin levels, and the pancreatic tissue was excised for histopathologic confirmation of pancreatitis. Plasma leptin rose significantly from the median of 0.78 ± 0.12 ng/ml in the control group to 1.92 ± 0.10 ng/ml and 1.86 ± 0.13 ng/ml in acute and chronic pancreatitis groups, respectively (p < 0.001, for both). There was no significant difference in the plasma leptin levels between the acute pancreatitis group and the chronic pancreatitis group (p > 0.05). These findings confirm that leptin has a role in pancreas inflammation, and the inflamed tissue can be the source of local production of leptin.
Mild persistent asthma is most effectively controlled with inhaled corticosteroids. Leukotriene receptor antagonists have complementary effects to corticosteroids on inflammation control. The additional effect of a leukotriene receptor antagonist, zafirlukast, was investigated in stable asthma patients under control with inhaled budesonide. We conducted a randomised, double-blind, placebo-controlled, single center trial to investigate the effects of add-on zafirlukast treatment to budesonide, on symptom score, pulmonary function, bronchial responsiveness, and serum levels of eosinophilic cationic protein (ECP) and antioxidant capacity in stable asthmatic patients under control with inhaled budesonide. The present study included 21 mild or moderate asthmatic patients (8 males and 13 females), who were stable at least for 6 weeks with inhaled budesonide (400 μg/day). Serum total antioxidant capacity (TAC) and ECP levels were measured, and symptom scoring, spirometry, and bronchial provocation with methacholine were performed. Then, the patients were randomised to use either placebo or oral zafirlukast (40 mg/day) in addition to budesonide for 6 weeks. At the 6th week, symptom scoring, spirometry, and bronchial provocation tests were repeated and serum TAC and ECP levels were measured again. After add-on zafirlukast treatment to budesonide, forced expiratory volume in 1 second (FEV1), TAC and ECP values did not change significantly (p > 0.05) but bronchial hyperresponsiveness and symptom score decreased significantly (p = 0.022) compared to baseline. Thus, in stable asthmatic patients, add-on zafirlukast treatment to budesonide improves symptoms and decreases bronchial hyperresponsiveness.
Dexamethasone (DEX) suppresses the secretion of and responsiveness to growth hormone (GH). Here we aimed to assess the therapeutic effects of GH on the DEX-induced osteopenia. Female Wistar rats were treated for 2 weeks with DEX (200 μg/day) or saline as a control. DEX significantly decreased body weight gain, bone mineral density (BMD), growth plate thickness, area ratio of trabecular bone, and serum osteocalcin levels. DEX also elongated the tibia primary spongiosa and caused many tiny lipid droplets in the tibia marrow. These results indicated that DEX induced osteopenia in rats. We then assessed the effects of GH on the recovery of osteopenia after withdrawal of DEX. DEX-treated rats were subsequently treated for 1 week with GH (0.1 or 0.3 U/day) or saline, while saline-pretreated rats were treated for 1 week with saline as a control. GH (0.1 or 0.3 U/day)-treated rats showed a catch-up growth in various bone measurements by one week after DEX withdrawal, though most of them remained subnormal. GH treatment did not enhance the recovery of DEX-induced osteopenia. Therefore a short-term exposure to DEX significantly impaired the bone metabolism, which started to recover soon after withdrawal of DEX. Unfortunately, immediate administration of GH after withdrawal of DEX did not enhance the recovery process.
Obstructive sleep apnea syndrome (OSAS) is defined as intermittent complete or partial upper airway obstruction during sleep, causing mental and physical effects. Both the local and systemic inflammation observed in OSAS induce certain potent pro-inflammatory mediators, which may contribute to the development of cardiovascular consequences. The present study was designed to evaluate the plasma levels of TNF-α, which is one of the known pro-inflammatory cytokines, in patients with OSAS and to assess the effect of surgical treatment on the levels of TNF-α levels. Twenty seven patients diagnosed to have OSAS, 7 non-apneic patients with chronic tonsillitis (non-OSAS patients), and 4 healthy subjects were enrolled in this study. Blood samples were collected one week preoperatively and postoperatively, and the plasma TNF-α levels were measured using high-sensitivity ELISA. The plasma TNF-α levels in patients with OSAS were significantly elevated in comparison to normal healthy subjects. In contrast, there was no difference between the patients with non-OSAS and healthy subjects. Moreover, the surgical treatment to enlarge the upper airway in patients with OSAS significantly decreased the levels of TNF-α levels. Surgical treatment of patients with OSAS reduces the plasma TNF-α levels, thereby ameliorating the systemic inflammation and preventing the development of cardiovascular consequences.
Although it has been argued that those with lower levels of serum cholesterol are likely to be depressive, the findings are inconsistent. The present study attempted to clarify the relationship between major depression and serum total cholesterol in a working population. Subjects were 987 Japanese men working at an institute, aged 20 to 64 years. In addition to blood examinations and physical measurements, clinical structured interviews of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) were used to detect major depression. The prevalence of major depression was higher in the hypercholesterolemics (serum total cholesterol levels ≥ 5.69 mmol/liter) than in the normocholesterolemics (3.10-5.69 mmol/liter) (6.1% vs 1.8%, p < 0.05). Notably, there was no case with major depression among the hypocholesterolemics (< 3.10 mmol/liter). Through a multiple regression analysis, serum total cholesterol levels were positively predicted by the following four variables: major depression, age, body mass index, and skipping breakfast (all p < 0.01). Concerning those diagnosed with major depression, serum total cholesterol levels remained higher in the following year (p < 0.05), comparing to those without such diagnosis. Therefore, depression is associated with higher serum cholesterol levels in a population of Japanese male workers. The irregularity of eating behavior may be one of the factors mediating high serum cholesterol levels and major depression.
Expression of inflammatory cytokines derived from Th1 cell population is increased in patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been shown that cytokine signaling molecules, including transcription factors T-bet and GATA-3, interleukin-12 receptor β2 (IL-12Rβ2) and suppressors of cytokine signaling (SOCS), such as SOCS1, are important in differentiation of naive T cells into Th1 helper T cells. To assess the immunological status from the stand-point of cytokine signaling in patients with HAM/TSP, we analyzed mRNA expression of these cytokine signaling molecules in peripheral blood mononuclear cells using quantitative RT-PCR. Twenty-eight HAM/TSP patients, nine HTLV-I-infected individuals without HAM/TSP and twenty-two HTLV-I-uninfected individuals were included in this study. Expression of T-bet, GATA-3, IL-12Rβ2 and SOCS1 was significantly increased in HAM/TSP patients in comparison with HTLV-I-uninfected individuals. In contrast, expression of SOCS3, a marker for Th2 cells, was significantly decreased in HTLV-I-infected individuals. These results indicate that HAM/TSP patients are associated with increased Th1 and decreased Th2 cytokine signaling activities.
Hypolipidemic drugs are potent serum cholesterol lowering agents used for prevention of coronary heart disease. In addition to their cholesterol lowering effect, these drugs exhibit both pleiotropic beneficial and various neurological side effects. Therefore, we analysed effect of the hypolipidemic drugs, fenofibrate and statins, on membrane lipid composition in the rat brain tissue. Male Wistar rats were given 0.1 mg of fenofibrate, lovastatin, pravastatin, fluvastatin or placebo (control) once daily for six weeks. In rats treated with lovastatin or pravastatin, decreased cholesterol and increased ceramide monohexoside contents in the brain tissue were observed in comparison with control. Treatment with fluvastatin or lovastatin resulted in increased sphingomyelin and decreased diphosphatidylglycerol contents. The most important changes in the fatty acid profile were observed in ceramide monohexosides; treatment with fluvastatin decreased the content of saturated and increased the content of polyunsaturated fatty acids. Fenofibrate treatment led to decreased content of saturated fatty acids in phosphatidylethanolamines. In conclusion, statin treatment resulted in the decreased content of cholesterol and diphosphatidylglycerol associated with the increased content of sphingolipids in the rat brain tissue. As cholesterol and sphingolipids are important components of brain membranes, the observed alterations in the composition brain lipids might be involved in genesis of neurological and mental symptoms following statin therapy.
Combination chemotherapy consisting of bleomycin, ifosfamide, and ciplatin (BIP) is recognized as one of the most effective chemotherapies for uterine cervical cancer. However, there have been no reports that evaluate concurrent use of radiation with BIP. The objective of this study was to evaluate the toxicity and response of the combination of BIP concurrent with radiation in patients with squamous cell carcinoma of the uterine cervix. Eligibility criteria included patients who underwent radical hysterectomy (Type III hysterectomy) as a primary treatment and revealed lymph node metastases or deep myometrial invasion (stage IB and IIA) and patients who were previously untreated (stage IIB-IV). All of the patients had biopsy-proven squamous cell carcinoma of the uterine cervix. The patients received three courses of BIP chemoradiation, and the response and toxicity were evaluated. From January 2000 to December 2003, 30 patients met study eligibility criteria. All but three patients completed 3 courses of planned chemotherapy. The frequency of severe (grade 3 and 4) toxicity was as follows: anemia, 46.7%; neutrocytopenia, 73.3%; thrombocytopenia, 16.7%; and nausea and vomiting, 23.3%. Among 30 patients, 22 cases were evaluated for response. Complete response was achieved in 16 (72.7%) of patients, with a response rate of 90.9%. In conclusion, BIP chemoradiation seems to be superior to previously reported chemoradiation regimens, and has a potential as an optimal combination chemotherapy concurrent with radiation.
Medulloblastoma is a malignant invasive embryonal tumor of the cerebellum with preferential manifestation in children. The peak of occurrence is seven years of age. Seventy percent of medulloblastomas occur in individuals younger than 16. In adulthood, 80% of medulloblastomas arise in the 21-40 years age group. A 48-year-old male patient was admitted to the hospital with complains of headache, ataxia, morning vomitting and difficulty in speech was operated with the diagnosis of presence of mass of 4 × 7 cm size retaining a diffuse homogenous contrast in the posterior fossa. The diagnosis of desmoplastic medulloblastoma was given after histopathological examination. Immunohistochemical examination revealed that neoplastic cells showed staining with neuron-specific enolase and synaptophysin but not with glial fibrillary acidic protein. This lesion showed nodular, reticulin free-zones (pale islands) surrounded by densely packed, highly proliferative cells. The pale regions within the tumor did not contain reticulin fibers. Desmoplastic medulloblastoma is encountered especially in adulthood. This type of tumor rarely occurs beyond the fifth decade of life. We present a case of desmoplastic medulloblastoma in a 48-year-old male.