Early neonatal inflammation affects adult pain reactivity and anxiety related traits in mice: genetic background counts

Protracted or recurrent pain and inflammation in the early neonatal period may cause long-lasting changes in central neural function. However, more research is necessary to better characterize the long-term behavioral sequelae of such exposure in the neonatal period. Objectives: (1) to study whether timing of postnatal exposure to persistent inflammation alters responsiveness to thermal pain in the adult animal; (2) to assess whether animals experiencing early postnatal chronic inflammation display altered anxiety related behavior; (3) to study the importance of genetic background. Newborn mice (outbred strain, CD1 and F1 hybrid strain, B6C3F1) received an injection of Complete Freund's Adjuvant (CFA) or saline on either postnatal day 1 or 14 (PND1; PND14) into the left hind paw. Pain to radiant heat and anxiety were examined in 12-week-old adult animals. Adult baseline PWL was significantly decreased in CD1 mice exposed to CFA on PND 1 and 14 as compared to their saline treated counterparts. B6C3F1 mice exposed to CFA on PND14 showed markedly reduced baseline PWL compared to the PND14 saline group. Persistent inflammation experienced by B6C3F1 mice on PND1 failed to affect baseline adult thermal responsiveness. Adult mice, CD1 and B6C3F1, displayed low anxiety traits only if they had been exposed to persistent inflammation on PND1 and not on PND14. Our research suggests a role for genetic background in modulating long-term behavioral consequences of neonatal persistent inflammation: the data support the hypothesis that pain experienced very early in life differentially affects adult behavioral and emotional responsiveness in outbred (CD1) and hybrid mice (B6C3F1).     

Thyrotrophin-Releasing Hormone Raises Cytosolic Free Calcium Concentration in Human Adenomatous Somatotrophs and Corticotrophs; Comparison with in vivo Responsiveness to Thyrotrophin-Releasing Hormone in Patients with Acromegaly or Cushing's Disease

The effect of thyrotrophin-releasing hormone (TRH) on intracellular free Ca²⁺ concentration, [Ca²⁺)i, was investigated with the fluorescent dye fura-2 in cell suspensions obtained from 13 human growth hormone-secreting adenomas and 6 adrenocorticotrophin-secreting adenomas. Preoperatively, 9 out of 13 acromegalic patients showed a positive growth hormone response to TRH administration while none of the 6 patients with Cushing's disease had a plasma adrenocorticotrophin increase after TRH injection. In all the growth hormone-secreting adenomas the addition of TRH (100 nM) caused a significant rise in [Ca²⁺]i (from a resting level of 133±40 (±SD) to a value of 284±119 nM at 100 nM TRH, n = 42; P<0.001). The transient induced by TRH was found to have a dual origin, one due to Ca²⁺ mobilization from intracellular stores which was maintained in presence of EGTA (3mM) and verapamil (10 μM) and a plateau phase due to Ca²⁺ influx from the extracellular media. Somatostatin (0.1 μM) lowered both resting [Ca²⁺]i and TRH-induced transients. The effect of gonadotrophin-releasing hormone on [Ca²⁺]i was evaluated on cell suspensions obtained from 6 growth hormone-secreting adenomas. Gonadotrophin-releasing hormone (100 nM) caused a marked rise in [Ca²⁺]i (from 179±25 to 283±15nM) on the cell suspension obtained from the only in vivo responsive adenoma while it was ineffective in the remaining 5. Although TRH was ineffective in modifying plasma adrenocorticotrophin levels in all patients with Cushing's disease, in 5 out of 6 tumors the addition of 100 nM TRH caused a significant rise in [Ca²⁺]i (from 102.5 ± 36 to 163±66 nM, n = 22; P < 0.005). However, the effect of TRH on [Ca²⁺]i was significantly lower than that caused by arginine vasopressin, a physiological stimulator of adrenocorticotrophin release ([Ca²⁺]i values; 145±78 nM at 100 nM TRH versus 300±140 at 10 nM arginine vasopressin, n = 15; P<0.05). Moreover, the effect of arginine vasopressin on [Ca²⁺]i was detectable at concentrations as low as 0.1 nM while TRH was effective at concentrations higher than 1 nM. By contrast, gonadotrophin-releasing hormone was ineffective in increasing [Ca²]i in all the adrenocorticotrophin-secreting adenomas studied. Collectively, these data indicate that sensitivity to TRH is present in almost all the growth hormone- and adrenocorticotrophin-secreting adenomas independently of the responsiveness of the individual patients to the peptide.     

N-ω-Carbethoxypentyl-4-quinolones: A New Class of Leukotriene Biosynthesis Inhibitors

6-[(4-Quinolinyl)oxy]hexanoic acids and the corresponding esters were designed and synthesized as inhibitors of the production of arachidonic acid metabolites. The inhibitory activities were assayed in vitro by evaluation of serum leukotriene B₄ and thromboxane B₂ production. While all 6-[(4-quinolinyl)oxy]hexanoic acids and their esters proved to be inactive, the N-alkyl-4-quinolones, obtained as by-products in their synthesis, were found to be a new class of leukotriene biosynthesis inhibitors.     

Transvaginal sonographic appearance of peritoneal pseudocysts.

OBJECTIVE: To describe the sonographic features of peritoneal pseudocysts (PPCs) in order to determine the particular aspects that distinguish them from true ovarian cysts. METHODS: Thirty-one women with PPCs were investigated using transvaginal sonography immediately before surgery. The diameters of the cysts were measured, and the shape, margins, content, location, presence of septa and echogenic portions were analyzed. RESULTS: The PPCs were monolateral in 20 (65%) and bilateral in 11 (35%) women. A well-defined cystic structure was found in only six (19%) women, while in the other 25 (81%) women the PPCs showed blurred, undefined margins and a bizarre morphology, giving them a star-like tubular or lumpy shape. The ipsilateral ovary was identified in 26 (84%) cases either external to the cyst or entrapped within it like a 'spider in a web'. Septa were present in 25 (81%) cases and were often mobile, resembling a 'flapping sail' when touched by the endovaginal probe. CONCLUSION: Despite having a gross morphology resembling that of a true ovarian cyst, PPCs present some characteristic sonographic findings that allow a correct differential diagnosis in the vast majority of cases.     

The clinical phenotypes of juvenile bipolar disorder: toward a validation of the episodic-chronic-distinction.

BACKGROUND: Recent research has addressed the issue of subtyping juvenile bipolar disorder (JBD). Accordingly, we set out to find out, in a naturalistic sample of bipolar children and adolescents with mania and mixed mania, whether the most useful subtyping should be based on clinical features (elated vs. irritable) or course (episodic vs. chronic). METHODS: We studied 136 patients, 81 male patients (59.6%) and 55 female patients (40.4%), mean age 13.5 +/- 2.9 years, meeting the DSM-IV diagnosis of bipolar disorder, assessed by a structured clinical interview (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version [K-SADS-PL]). RESULTS: Regarding course, 77 patients (56.6%) had an episodic course and 59 patients (43.4%) had a chronic course. Patients with chronic course were significantly younger, had an earlier onset of JBD, and presented a more frequent comorbidity with disruptive behavior disorders. According to the prevalent mood disturbance, 75 patients (55.1%) showed an elated and 61 patients (44.9%) showed an irritable mood. Elated mood was more frequent in patients with episodic course, whereas irritable mood was more frequent in the patients with chronic course. CONCLUSIONS: These findings suggest that chronic versus episodic course may be a putative differential feature. Further validation of such a distinction would require prospective studies, temperament evaluation, gender and neurobiologic approaches, and differential psychopharmacologic assignment and response.     

Epidemiological study of myasthenia gravis in Sardinia, Italy (1958–1986)

From 1.1.1958 to 31.12.1986, 110 cases of MG were observed in Sardinia, with a mean annual incidence of 2.5 x 1,000,000 inhabitants and prevalence rates of 7.5, 17.6, 31.4 and 45.0 x 1,000,000 inhabitants respectively (prevalence days: 15.10.1961, 24.10.1971, 25.10.1981 and 31.12.1986). The disease was found to be more frequent in women. There were no differences in the distribution of MG in various areas of the island. The muscle group more frequently involved at onset was the ocular. In 6.4% of patients an association with thyroid disorders was observed. The mortality of MG patients was significantly higher than expected. Removal of the thymus, carried out in 58 patients, was shown to be useful in the treatment of the disease, particularly in patients without thymomas. No familial cases were observed.