Translocation of Akt/PKB to the nucleus of osteoblast-like MC3T3-E1 cells exposed to proliferative growth factors.

An active phosphatidylinositol 3-kinase (PI3K) has been shown in nuclei of different cell types. The products of this enzyme, i.e. inositides phosphorylated in the D3 position of the inositol ring, may act as second messengers themselves. Nuclear PI3K translocation has been demonstrated to be related to an analogous translocation of a PtdIns(3,4,5)P(3) activated PKC, the zeta isozyme. We have examined the issue of whether or not in the osteoblast-like clonal cell line MC3T3-E1 there may be observed an insulin-like growth factor-I- (IGF-I) and platelet-derived growth factor- (PDGF) dependent nuclear translocation of an active Akt/PKB. Western blot analysis showed a maximal nuclear translocation after 20 min of IGF-I stimulation or after 30 min of PDGF treatment. Both growth factors increased rapidly and transiently the enzyme activity of immunoprecipitable nuclear Akt/PKB on a similar time scale and after 60 min the values were slightly higher than the basal levels. Enzyme translocation was blocked by the specific PI3K inhibitor, LY294002, as well as cell entry into S-phase. Confocal microscopy showed an evident increase in immunostaining intensity in the nuclear interior after growth factor treatment but no changes in the subcellular distribution of Akt/PKB when a LY294002 pre-treatment was administered to the cells. These findings strongly suggest that the intranuclear translocation of Akt/PKB is an important step in signalling pathways that mediate cell proliferation.

Free zinc increases at the site of injury after cortical stab wounds in mature but not immature rat brain.

The accumulation of free zinc (Zn2+) appears to play a role in the neuronal degeneration that occurs after brain injury. Given that neonates respond to brain injury with increased plasticity compared to adults, this study compared the effect of age on free Zn2+ and the Zn2+-binding protein metallothionein-3 (MT-3) after injury. Unilateral cortical stab wounds were produced in 3-day-old and adult rats. Four weeks later, brains were removed for in situ visualization of free Zn2+ and measurement of MT-3 mRNA. Free Zn2+ and MT-3 mRNA accumulated after 4 weeks at the site of injury site when injury occurred in adults. However, 4 weeks after neonatal injury there was no increase in free Zn2+ or MT-3 mRNA in or around the site of injury.

Effects of central leptin administration on blood pressure in normotensive rats.

We tested the hypothesis that intracerebroventricular (i.c.v.) administration of leptin would increase mean arterial pressure (MAP) in ad libitum (AL) fed and food deprived (FD) normotensive rats. Male Sprague-Dawley rats were chronically instrumented with a guide cannula directed at the lateral ventricle and a carotid arterial catheter. Following recovery from surgery, the MAP and heart rate (HR) response to i.c.v. administration of vehicle (5 microl saline over 1 min) or leptin (0.3 microg or 3.0 microg in 5 microl saline) were determined in conscious, unrestrained AL fed (n=7-10) and 48-h FD (n=5-10) rats. Food deprivation significantly reduced MAP (AL=116+/-3; FD=104+/-3 mmHg; P < 0.01) without altering HR. In AL rats, high dose leptin (3.0 microg, i.c.v.) produced a significant increase in MAP when maximal responses were evaluated (9+/-2 mmHg; P < 0.05), but did not significantly alter MAP and HR over time during the 90 min measurement period. In FD rats, low dose leptin (0.3 microg, i.c.v.) produced significant elevations in MAP (7+/-3 mmHg) after a latency of 60 min, while high dose leptin (3.0 microg, i.c.v.) produced an increase in MAP within the first 10 min (10+/-3 mmHg) followed by an additional increase 1 h after injection (6+/-2 mmHg). Leptin administration also produced delayed increases in HR in FD rats (0.3 microg, 34+/-5 b.p.m.; 3.0 microg, 57+/-10 b.p.m). These results indicate that leptin may modulate cardiovascular function through central mechanisms and may do so to a greater extent in food deprived animals.

Food restriction attenuates the blood pressure response to paraventricular hypothalamic nuclei lesions in aortic coarctation hypertension.

Chronic food restriction reduces blood pressure (BP) and sympathetic support of BP in aortic coarctation hypertension. The purpose of this study was to test the hypothesis that chronic food restriction would reduce sympathetic support of BP mediated by the paraventricular hypothalamic nuclei (PVN). Hypertension was induced in male Sprague-Dawley rats (n=40) by suprarenal aortic coarctation. Rats were assigned to either an ad libitum fed (AL) group or a food restricted (FR) group that received 60% of the food consumed by AL for 3 weeks. One week prior to data collection, catheters were implanted in the left carotid artery and right jugular vein. BP was measured for 2 days prior to, and 7 days after rats in AL and FR groups received either bilateral electrolytic lesions of the PVN (PVNx) or sham lesions (SHAM). Prior to either PVNx or SHAM, FR rats had significantly lower BP (AL=152+/-5; FR=113+/-2 mmHg), less of a depressor response to ganglionic blockade (AL=-58+/-4; FR=-35+/-2 mmHg), and lower plasma norepinephrine levels (AL=758+/-71; FR=380+/-23 pg/ml) compared to AL. PVNx reduced BP in both AL and FR rats (AL-PVNx=105+/-6 mmHg, FR-PVNx=101+/-3 mmHg). PVNx also lowered the depressor response to ganglionic blockade (AL-PVNx=-28+/-5 mmHg, FR-PVNx=-29+/-4 mmHg) and plasma norepinephrine levels (AL-PVNx=372+/-74 pg/ml, FR-PVNx=248+/-31 pg/ml). FR decreased the magnitude of the reductions in resting BP and in sympathetic activity in response to PVNx. These results indicate that intact PVN are required for maintenance of aortic coarctation hypertension, and implicate the PVN as a site involved in BP reductions produced by chronic food restriction.

Antihypertensive effects of food-intake restriction in aortic coarctation hypertension.

OBJECTIVE: To test the hypothesis that reductions in mean arterial pressure (MAP) induced by food-intake restriction in aortic coarctation hypertension are the result of a reduction of the sympathetic support of the MAP. We also wanted to determine whether the baroreflex control of the heart rate, and alpha- and beta-adrenergic responsivenesses were influenced by chronic food-intake restriction. METHODS: Four days after aortic coarctation, female Sprague-Dawley rats were assigned to a group that had access ad libitum to food (CON; n = 19) or to a food-intake-restricted group (FRG; n = 17) that was allowed 60% of the CON group's food intake per rat. After 3 weeks, carotid and jugular catheters were implanted for measurement of the MAP and infusion of drugs into conscious rats. The sympathetic contribution to the blood pressure was assessed by measuring the depressor response to ganglionic blockade by hexamethonium plus atropine (30.0 and 0.1 mg/kg intravenously). The baroreflex control of the heart rate was assessed by administering alternating bolus doses of phenylephrine and nitroprusside. The alpha-adrenergic sensitivity was assessed by measuring the response of the MAP to phenylephrine in areflexive rats (after ganglionic blockade), and the beta-adrenergic sensitivity was assessed by measuring the responses of the MAP and heart rate to isoproterenol administration both in reflexive and in areflexive rats. RESULTS: Four days after catheterization, both the MAP (CON 150 +/- 5 mmHg, FRG 116 +/- 4 mmHg) and the heart rate (CON 414 +/- 8 beats/min, FRG 365 +/- 11 beats/min) were significantly lower in rats of the FRG. That the sympathetic support of the MAP had diminished in FRG rats was evidenced by an attenuated depressor response to ganglionic blockade (40 +/- 3 versus 65 +/- 3 mmHg). FRG rats exhibited significantly greater reflex bradycardia in response to phenylephrine (slope -1.44+/- 0.07 versus -0.54 +/- 0.05 beats/min per mmHg), whereas their reflex tachycardia was not altered (slope -1.58 +/- 0.08 versus -1.53 +/- 0.13 beats/min per mmHg). FRG rats also displayed blunted responses of the heart rate and MAP to isoproterenol administration. CONCLUSION: Food-intake restriction attenuates the rise in MAP which occurs after aortic coarctation significantly. The antihypertensive effect of food-intake restriction may be mediated via a reduction in sympathetic tone.

Food restriction reduces sympathetic support of blood pressure in spontaneously hypertensive rats.

We tested the hypothesis that food restriction would attenuate the development of hypertension in spontaneously hypertensive rats (SHR). Furthermore, we hypothesized that food restriction would reduce the tonic sympathetic nervous system support of blood pressure in the SHR. Male SHR (Charles River, age 5 wk) were randomly assigned to ad libitum (ADLIB, n = 8) or food-restricted (FR, n = 9) groups. ADLIB rats were given free access to nonpurified diet and demineralized water. Food-restricted rats ate 60% of the amount of nonpurified diet consumed by rats in the ADLIB group. After 8 wk of treatment, ADLIB rats were heavier than FR rats (ADLIB = 318 +/- 4 g; FR = 193 +/- 5 g, P < 0.05). Blood pressure and heart rate (HR) were measured after chronic implantation of iliac arterial and jugular venous catheters. Food-restricted rats had lower mean arterial blood pressure (MAP) than ADLIB rats, measured in conscious, unrestrained state 4-6 h after catheterization (ADLIB = 162 +/- 3 mmHg; FR = 142 +/- 3 mmHg, P < 0.05) and measured on the day after surgery (ADLIB = 150 +/- 6 mmHg; FR = 130 +/- 3 mmHg, P < 0.05). There were no significant differences in resting HR on either day. Food-restricted rats exhibited augmented cardiac baroreflex-mediated bradycardia (bolus phenylephrine, 0.5-4.0 pg/kg intravenously) as assessed by linear slope of the AHR/AMAP relationship (ADLIB = -0.73 beats/(min x mmHg); FR = -1.62 beats/(min x mmHg), P < 0.05). Sympathetic support of blood pressure quantified by the depressor response to ganglionic blockade (hexamethonium 30 mg/kg; atropine 0.1 mg/kg intravenously), was greater in the ADLIB group (ADLIB: -59 +/- 8 mmHg; FR: -36 +/- 2 mmHg, P < 0.05). The results support the hypotheses that chronic food restriction reduces the development of hypertension and sympathetic support of MAP in spontaneously hypertensive rats.

[Choledochal calculosis due to a suture thread]. / Calcolosi coledocica da filo di sutura.

The authors recently observed a patient suffering from recurrent choledochal, postcholecystectomy calculosis caused by suture thread. Given the relative rarity of this pathology, the difficulty of preoperative diagnosis and the possible confusion with other anatomoclinical syndromes, they take this opportunity to make a number of diagnostic and therapeutic comments in the light of the latest literature on this subject.

[Role of surgery in the treatment of gastroduodenal ulcer]. / Ruolo della chirurgia nel trattamento dell'ulcera gastroduodenale.

Medical approach to gastroduodenal ulcer has dramatically changed with the advent of anti-H2 drugs. There is still a role for surgery, but it has been confined to the treatment of the complications (perforation, stenosis and some cases of haemorrhage). In this paper the Authors collected the data of 43 patients (27 males and 16 females, mean age 45), operated between July 1988 and December 1992; 12 patients were operated for pyloric stenosis, 16 for gastrointestinal bleeding and 15 for perforation. Surgery was accomplished as an emergency procedure in 20 cases, delayed emergency procedure in 4 cases and elective procedure in 19 cases. 39 out of 43 patients were under anti-H2 treatment for a previous diagnosis of peptic ulcer. In conclusion, anti-H2 therapy, even correctly carried on, may not be effective in avoiding possible complications. This goal may be obtained in patients under omeprazole treatment.

[Carcinoma of the rectum. Considerations on diagnosis and therapy]. / Il carcinoma del retto. Considerazioni in tema di diagnosi e terapia.

In this review the authors after an introduction on the risk factors, the symptoms and diagnostic aspects of rectal carcinoma, show the different surgical techniques, used second the literature and personal experience on 37 cases for the upper, middle and lower neoplastic lesions of the rectum.

The stereospecific effects of isoflurane isomers in vivo.

The anesthetic potency of racemic isoflurane and the optically pure stereoisomers was examined in rats. The (+) isomer was 53% more potent than the (-) isomer (minimum alveolar concentration (MAC) = 1.06 +/- 0.07% vs. 1.62 +/- 0.02%, P < 0.05). MAC for racemic isoflurane was 1.32 +/- 0.03%. Both stereoisomers and the racemic isoflurane produced similar depression of arterial pressure. However, the (+) isomer blunted the cardiovascular response to a painful stimulus to a greater extent than did an equi-MAC dose of the (-) isomer. These are the first data to describe pharmacological differences between stereoisomers of a volatile anesthetic administered in vivo by the conventional route (inhaled) and measuring the clinically relevant index of anesthesia, MAC. These data are consistent with a receptor-mediated anesthetic mechanism by volatile anesthetics.

[Chronic anemia due to Meckel's diverticulum. The diagnostic and therapeutic considerations]. / Anemia cronica da diverticolo di Meckel. Considerazioni diagnostico-terapeutiche.

Meckel's diverticulum is a frequent embryologic residual organ. The importance of considering this diagnosis in the young adult presenting chronic hypochromic [correction of hyperchromic] anemia, despite the difficulties of the same, is emphasized. The condition to be satisfied is the complete excision of Meckel's diverticulum, to avoid leaving ectopic mucosa residuals, so we think it useful to resect an ileal sleeve.

[The surgical treatment of a rare pulmonary infection: mucormycosis]. / Trattamento chirurgico di una rara infezione polmonare: la mucormicosi.

Pulmonary mucormycosis (phycomycosis) is an uncommon infection occurring in immunodepressed or debilitated patients. Mortality is very high. Recovery depends upon underlying disease and upon early diagnosis, although difficult to obtain. Aggressive medical therapy is requested and surgical treatment in some instances is indicated. The following is a report of pulmonary mucormycosis occurring in a man with lymphocytic leukemia under chemotherapy treatment. Surgical treatment was considered as medical treatment had been unsuccessful. No success has been achieved, as also diffuse bone metastases showed up.

On the role of renal alpha-adrenergic receptors in spontaneously hypertensive rats.

We tested the hypothesis that a genetically determined increase in renal alpha-adrenergic receptor density might be a pathophysiologically important factor in the spontaneously hypertensive rat model of genetic hypertension. In a first study, we compared renal alpha 1 and alpha 2-adrenergic receptor density with systolic blood pressure in 45 rats of an F2 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids but were unable to detect significant cosegregation between either receptor density or blood pressure. In a second study, we determined renal alpha 1- and alpha 2-adrenergic receptor density in Wistar-Kyoto and spontaneously hypertensive rat kidneys that were transplanted into an F1 generation of Wistar-Kyoto x spontaneously hypertensive rat hybrids. Although Wistar-Kyoto kidneys lowered blood pressure in these animals and spontaneously hypertensive rat kidneys increased blood pressure, renal alpha-adrenergic receptor densities were similar in membranes from both types of kidneys. Since rat kidney coexpresses alpha 1A- and alpha 1B-adrenergic receptors, we also investigated whether differential regulation of these two subtypes might conceal ongoing alterations. The alpha 1A/alpha 1B-adrenergic receptor ratio, however, was similar in Wistar-Kyoto rats, spontaneously hypertensive rats, and F1 rats transplanted with a kidney from either strain. Taken together these data do not support the hypothesis that genetically determined alterations of renal alpha-adrenergic receptor numbers play an important role in the development of elevated blood pressure in the spontaneously hypertensive rat.

[Intrahepatic jejunostomy by trans-scission approach in neoplasms of the superior biliary confluent (SBC)]. / Intraepatico-digiunostomie per via trans-scissurale per neoplasie del confluente biliare superiore (CBS).

The Authors consider the trans-scission approach as a quick and safe alternative approach for doing intrahepatic bilio-intestinal anastomoses for the surgical treatment of well confined cancers of hepatic hilus (type I and II of Bismuth e Corlette). This approach should be recommended particularly when the presence of anatomical variations makes the hilar approach hazardous.

[Pulmonary metastases. Their diagnosis and surgical therapy]. / Le metastasi polmonari. Diagnosi e terapia chirurgica.

The Authors on the basis of their own experience and scientific literature, study the indications to the surgical treatment of pulmonary metastasis. Surgical treatment usually produces a palliative result, bettering the quality of life. For some other Authors, surgical treatment if there are no local recurrences and metastasis, could produce complete healing.

[An analysis of 100 consecutive mediastinoscopies for the diagnosis and/or staging of pulmonary carcinoma]. / Analisi di 100 mediastinoscopie consecutive per diagnosi e/o stadiazione del carcinoma del polmone.

The authors analyze data of 100 consecutive mediastinoscopies, performed for diagnostic and/or staging purposes in suspected or known bronchogenic carcinomas. They confirm once again how mediastinoscopy is, in many cases, the only diagnostic procedure that can give, at the same time, a preoperative histological diagnosis and a quite accurate staging, thus avoiding useless exploratory thoracotomies.

Dissociation of tactile and acoustic components in air puff startle.

Tactile (air puff) or acoustic startle stimuli elicit behavioral (motor) and complex cardiovascular responses which include pressor as well as cardiac decelerative and accelerative responses. An acoustic component of the air puff stimulus (12.5 psi) was identified. Studies were conducted to separate the contributions of both stimulus modalities to the observed responses. The acoustic component was approximated with a wide-spectrum 97-dB white-noise stimulus. This acoustic stimulus failed to evoke heart rate responses but did yield motor and pressor responses. In a second approach, tympanic membrane rupture (TMR) was used to interrupt acoustic sensory stimuli. TMR fully abolished the motor and pressor responses to acoustic startle. With air puff startle, while TMR severely attenuated the motor response it only decreased slightly the pressor and cardiac accelerative responses and failed to influence the cardiac decelerative component. Our results indicate that air puff startle contains both tactile and acoustic modalities. Further, the motor response is largely driven by the acoustic modality since TMR abolished this response elicited by either acoustic or tactile stimulation. More importantly, motor and cardiovascular responses to startle may be separated through discrimination of afferent stimuli suggesting either differences in neural pathways for acoustic and tactile stimuli or a differential dependency of the various responses on stimulus characteristics.

[Soft-tissue sarcomas of the limbs at high risk of malignity. Current role of surgery and conservative treatment]. / Sarcomi ad alto rischio di malignità dei tessuti molli degli arti. Ruolo attuale della chirurgia e trattamento conservativo.

The authors discuss the role of surgical treatment in patients with highly malignant soft tissue sarcomas in the limbs. A careful analysis is made of different therapies on the basis of the results obtained by the authors and those reported in the literature. The anatomic classification of lesions is based on functional anatomic compartments, defined as intra- or extracompartmental. If a lesion was within an intrafascial compartment, all the muscles with intact fascial sheaths have up till now been removed "en bloc" to obtain radical margins. Many authors now think that all manifest disease be removed with a generous soft tissue margin on all sides to ensure adequate local treatment. Amputation has commonly been performed for extracompartmental lesions, but a multinodal treatment programme, including limb-sparing resection and tumour-bed radiation, should now be considered if possible in the management of these tumours.

Biometric genetic analysis of blood pressure in the spontaneously hypertensive rat.

The spontaneously hypertensive rat is the most widely studied animal model of essential hypertension, yet the genetics of transmission of high blood pressure in this strain have not been clearly defined. It has been proposed that in the spontaneously hypertensive rat, blood pressure follows a simple additive mode of inheritance and that the hypertension is primarily determined by a single major locus. To investigate the genetics of transmission of increased blood pressure in the spontaneously hypertensive rat, we performed a biometric genetic analysis of multiple, direct measurements of arterial pressure in unanesthetized, unrestrained rats derived by crossing spontaneously hypertensive rats with two different inbred normotensive strains, the Charles River Wistar-Kyoto rat and the Lewis rat. In both crosses, approximately 60% of the variation in blood pressure could be assigned to genotypic variation. The data fit an additive-dominance model of inheritance in which alleles decreasing blood pressure were partially dominant. Thus, in offspring derived from crosses between spontaneously hypertensive rats and Wistar-Kyoto rats or spontaneously hypertensive rats and Lewis rats that are raised under ordinary laboratory conditions, increased blood pressure is not determined by simple additive effects of alleles at a single major locus. The current findings are consistent with the possibility that in the spontaneously hypertensive rat, hypertension may arise from mutations in alleles that ordinarily act in a dominant fashion to suppress blood pressure.