Marijuana smoke induces severe pulmonary hyperresponsiveness, inflammation, and emphysema in a predictive mouse model not via CB1 receptor activation.

Sporadic clinical reports suggested that marijuana smoking induces spontaneous pneumothorax, but no animal models were available to validate these observations and to study the underlying mechanisms. Therefore, we performed a systematic study in CD1 mice as a predictive animal model and assessed the pathophysiological alterations in response to 4-mo-long whole body marijuana smoke with integrative methodologies in comparison with tobacco smoke. Bronchial responsiveness was measured with unrestrained whole body plethysmography, cell profile in the bronchoalveolar lavage fluid with flow cytometry, myeloperoxidase activity with spectrophotometry, inflammatory cytokines with ELISA, and histopathological alterations with light microscopy. Daily marijuana inhalation evoked severe bronchial hyperreactivity after a week. Characteristic perivascular/peribronchial edema, atelectasis, apical emphysema, and neutrophil and macrophage infiltration developed after 1 mo of marijuana smoking; lymphocyte accumulation after 2 mo; macrophage-like giant cells, irregular or destroyed bronchial mucosa, goblet cell hyperplasia after 3 mo; and severe atelectasis, emphysema, obstructed or damaged bronchioles, and endothelial proliferation at 4 mo. Myeloperoxidase activity, inflammatory cell, and cytokine profile correlated with these changes. Airway hyperresponsiveness and inflammation were not altered in mice lacking the CB1 cannabinoid receptor. In comparison, tobacco smoke induced hyperresponsiveness after 2 mo and significantly later caused inflammatory cell infiltration/activation with only mild emphysema. We provide the first systematic and comparative experimental evidence that marijuana causes severe airway hyperresponsiveness, inflammation, tissue destruction, and emphysema, which are not mediated by the CB1 receptor.

Feasibility of gadoxetate disodium-enhanced MR cholangiography in chronic cholestatic biliary disease.

AIM: To investigate the feasibility of gadoxetate disodium-enhanced magnetic resonance (MR) cholangiography in chronic obstructive cholestatic biliary disease in the clinical setting. MATERIALS AND METHODS: Twenty-three patients with dilated bile duct trees and ten volunteers underwent gadoxetate disodium-enhanced liver MR cholangiography and were enrolled in the present retrospective study. Gadoxetate disodium was given in a standardized manner as a bolus injection at a dose of 0.25 mmol/kg of body weight (0.1 ml/kg). Region of interest-based measurement of mean enhancement of the dilated bile ducts was performed in series before gadoxetate disodium administration and during hepatobiliary phases. RESULTS: Direct comparison of mean bile duct enhancement during hepatobiliary phases in the clinical imaging window between healthy volunteers [4.7 ± 2.2 arbitrary units (au)] and patients with dilated bile ducts (0.1 ± 0.3 au) revealed significantly lower or absent enhancement in dilated bile ducts (p = 0.001). CONCLUSION: Standard clinical gadoxetate disodium-enhanced MR cholangiography is not a reliable technique for the evaluation of the biliary trees, because of altered biliary gadoxetate disodium elimination in patients with chronic obstructive biliary diseases.

Over-dose insulin and stable gastric pentadecapeptide BPC 157. Attenuated gastric ulcers, seizures, brain lesions, hepatomegaly, fatty liver, breakdown of liver glycogen, profound hypoglycemia and calcification in rats.

We focused on over-dose insulin (250 IU/kg i.p.) induced gastric ulcers and then on other disturbances that were concomitantly induced in rats, seizures (eventually fatal), severely damaged neurons in cerebral cortex and hippocampus, hepatomegaly, fatty liver, increased AST, ALT and amylase serum values, breakdown of liver glycogen with profound hypoglycemia and calcification development. Calcium deposits were present in the blood vessel walls, hepatocytes surrounding blood vessels and sometimes even in parenchyma of the liver mainly as linear and only occasionally as granular accumulation. As an antidote after insulin, we applied the stable gastric pentadecapeptide BPC 157 (10 microg/kg) given (i) intraperitoneally or (ii) intragastrically immediately after insulin. Controls received simultaneously an equivolume of saline (5 ml/kg). Those rats that survived till the 180 minutes after over-dose application were further assessed. Interestingly, pentadecapeptide BPC 157, as an antiulcer peptide, may besides stomach ulcer consistently counteract all insulin disturbances and fatal outcome. BPC 157 rats showed no fatal outcome, they were mostly without hypoglycemic seizures with apparently higher blood glucose levels (glycogen was still present in hepatocytes), less liver pathology (i.e., normal liver weight, less fatty liver), decreased ALT, AST and amylase serum values, markedly less damaged neurons in brain and they only occasionally had small gastric lesions. BPC 157 rats exhibited mostly only dot-like calcium presentation. In conclusion, the success of BPC 157 therapy may indicate a likely role of BPC 157 in insulin controlling and BPC 157 may influence one or more causative process(es) after excessive insulin application.

Radiation-induced total regression of a highly recurrent giant perianal condyloma: report of case.

We report a case of a highly recurrent giant perianal condyloma, or Buschke-Lowenstein tumor, which was successfully treated by telecobalt therapy. We conclude that radiation therapy is an optional treatment modality for the management of giant perianal condylomata in selected cases.

Significance of bacterial translocation in nutrition.

Considerable progress has been made during the last decade in the understanding of the pathophysiology of sepsis and multiple organ dysfunction syndrome. Gut-derived sepsis has been recognized as an important etiology of multiple organ dysfunction syndrome. Bacterial translocation of indigenous intestinal flora to the systemic circulation has been postulated as an important etiology of gut-derived sepsis. In this paper, we review the fundamental aspects of bacterial translocation as mechanism of disease, and the influence of nutritional support. Critical animal and human data are presented and discussed, and emphasis is given to its potential clinical applications.

In vivo radioprotective effects of angiogenic growth factors on the small bowel of C3H mice.

This study was undertaken to determine if acidic or basic fibroblast growth factor (FGF1 or FGF2) or vascular endothelial growth factor (VEGF) alters the radiation response of small bowel after total-body irradiation (TBI). Female C3H mice were treated with various doses of angiogenic growth factor administered intravenously 24 h before or 1 h after TBI. Radiation doses ranged from 7 to 18 Gy. End points measured were the number of crypts in three portions of the small bowel, the frequency of apoptosis of crypt cells at various times after TBI, and the LD50/30 (bone marrow syndrome) and LD50/6 (GI syndrome). Fibroblast growth factors alone, without TBI, decreased the number of crypts per circumference significantly. Among the factors tested, FGF2 caused the greatest decline in baseline crypt number. Despite this decrease in the baseline crypt number, after irradiation the number of surviving crypts was greater in animals treated with growth factor. The greatest radioprotection occurred at intermediate doses of growth factor (6 to 18 pg/mouse). Mice treated with FGF1 and FGF2 had crypt survival curves with a slope that was more shallow than that for saline-treated animals, indicating radiation resistance of crypt stem cells in FGF-treated mice. The LD50/6 was increased by approximately 10% for all treatments with angiogenic growth factors, whether given before or after TBI. Apoptosis of crypt cells was maximum at 4 to 8 h after TBI. The cumulative apoptosis was decreased significantly in animals treated with angiogenic growth factors, and the greatest protection against apoptosis was seen in animals treated with FGF2 prior to TBI. All three angiogenic growth factors tested were radioprotective in small bowel whether given 24 h before or 1 h after irradiation. The mechanism of protection is unlikely to involve proliferation of crypt stem cells, but probably does involve prevention of radiation-induced apoptosis or enhanced repair of DNA damage of crypt cells.

[True splenic cyst treated with++videolaparoscopy. Case report and review of the literature]. / Cisto esplênico verdadeiro tratado por videolaparoscopia. Relato de caso e revisão da literatura.

True non-parasitic splenic cysts are uncommon, their real incidence is difficult to determine since over 30% are asymptomatic. Preoperatively these cysts are rarely diagnosed correctly and they are often findings on examinations. Partial or total splenectomy is the treatment of choice after ruling out splenic hydatidosis, since it is responsible for two thirds of global incidence. Currently, with the technological advances of surgery, especially of videolaparoscopy, some authors have proposed its use for partial cystectomy or splenectomy. The authors present the case of a true splenic cyst (epidermoid) which was resected videolaparoscopically and they discuss aspects of diagnosis and management.

Retrorectal tumors complicating pregnancy. Report of two cases.

PURPOSE: Retrorectal tumors are rare entities often found in females during reproductive age. Reports of retrorectal tumors complicating pregnancy are scant. This study presents two cases of retrorectal tumors complicating pregnancy and a literature review. METHODS: Two patients bearing retrorectal tumors diagnosed during pregnancy were referred to our care at the postpartum period. Both then underwent exploratory laparotomy. RESULTS: One patient had premature delivery by cesarean section because of hemorrhage from abruptio placentae followed by fetal mortality. Attempts to resect the tumor immediately after delivery had been unfruitful. The tumor was also unresectable on exploratory laparotomy. Biopsy studies of the tumor were consistent with low-grade myosarcoma. Another patient had a benign cystic mass that had been conservatively monitored throughout pregnancy. A healthy baby was delivered at term by cesarean section. The cyst was later resected via Kraske's incision and was diagnosed as cystic teratoma. CONCLUSIONS: Retrorectal tumors may cause significant local effects such as complicated pregnancy. Early detection in the population at risk is needed, as correct diagnosis and treatment may be done only on surgical exploration. During pregnancy, careful monitoring of advanced tumors is mandatory and may be sufficient to prevent maternal and fetal complications.

[Total regression of advanced gastric lymphoma after drug therapy]. / Regressão total de linfoma gástrico avançado após quimioterapia.

Primary gastric lymphoma is a relatively rare entity that may have several different methods of treatment, including surgery, chemotherapy and radiotherapy. We describe a case of advanced primary gastric lymphoma treated with chemotherapy. A 51-year-old male patient underwent total gastrectomy after two cycles of chemotherapy. The histologic examination of the gross specimen revealed total regression of the lymphoma. Literature review of this condition and a discussion about the diagnosis and treatment are presented.

Thermal injury induces very early production of interleukin-1 alpha in the rat by mechanisms other than endotoxemia.

BACKGROUND: Cytokines are putative mediators of thermal injury-induced systemic changes. We studied the effects of thermal injury on cytokine activation in vivo with a sensitive radioimmunoassay specific for rat interleukin-1 alpha (IL-1 alpha). METHODS: We characterized the organ distribution and expression kinetics of IL-1 alpha in rats submitted to either 20% total body surface area cutaneous burn, muscle burn, or endotoxic shock. Rats were killed at various time points, and liver, lung, spleen, ileum, thymus, kidney, skin, and plasma were harvested. Tissues were homogenized, and the supernates were assayed for rat IL-1 alpha. The assay detection limit was 1.5 ng/gm wet tissue (WT). RESULTS: Thermal injury induced marked elevations of IL-1 alpha levels in the liver and lung, and maximal levels were reached at 2.5 hours when compared with controls. In the liver mean IL-1 alpha levels in cutaneous burn injury were 16.5 +/- 6.2 ng/gm WT, whereas in sham injury they were 1.7 +/- 0.1 ng/gm WT, p < or = 0.05; in the lung IL-1 alpha levels with cutaneous burn injury were 10.3 +/- 1.3 ng/gm WT, whereas sham injury levels were 1.9 +/- 0.8 ng/gm WT, p < or = 0.002). Levels in all other organs and plasma were below detection limits. Muscle burn injury had similar elevated levels of IL-1 alpha in the liver at 1 hour, indistinguishable from cutaneous burn. In contrast, endotoxin challenge resulted in dramatic elevation of IL-1 alpha levels in all organs tested except for the kidney, whereas the skin maintained its usual large amounts of IL-1 alpha. CONCLUSIONS: These data indicate that thermal or mechanical injury induce very early and organ-specific association of IL-1 alpha in vivo by mechanisms other than endotoxemia.

Intestinal production of interleukin-1 alpha during endotoxemia in the mouse.

Interleukin-1 (IL-1) may be involved in gut permeability to macromolecules and gut glutamine metabolism during endotoxemia. We developed a sensitive radioimmunoassay specific for mouse IL-1 alpha (detection limit of 100 pg/ml, or 5 pM) and measured intestinal levels of IL-1 alpha in response to endotoxin. CD-1 mice (N = 190) were randomized to intraperitoneal (ip) or intravenous (i.v.) lipopolysaccharide (LPS) infusion (15 micrograms/g or 1.5 micrograms/g Escherichia coli 0111:B4 LPS) or saline. Mice were sacrificed at Time 0, 30 min, 1 hr, 2.5 hr, 4 hr, 6 hr, 12 hr, and 24 hr (3 mice/group/time point). Small bowel (SB) and large bowel (LB) were harvested and compared to liver. Duodenum, upper jejunum, midjejunum, terminal ileum, cecum, ascending colon, and sigmoid were analyzed in separate experiments. Tissues were frozen, weighed, and homogenized, the homogenates were centrifuged, and the supernates were assayed for immunoreactive IL-1 alpha. IL-1 alpha was expressed as pg/g wt +/- SEM (lowest detectable amount = 1000 pg/g wet tissue (WT)). SB but not LB from normal controls had constitutively elevated levels of IL-1 alpha (6177 +/- 1640 pg/g WT). LPS ip or i.v. produced lethargy, diarrhea, and a dramatic elevation of IL-1 alpha levels in both SB and LB. In SB, IL-1 alpha was elevated compared to baseline at 1 hr (19201 +/- 626 pg/g WT) and reached a fivefold maximal increase at 2.5 hr (31775 +/- 503 pg/g WT) following 15 micrograms/g ip.(ABSTRACT TRUNCATED AT 250 WORDS)

Cystic teratomas of the pancreas.

Cystic teratomas of the pancreas constitute an extremely rare entity with only nine cases, to our knowledge, described in the world literature. Symptoms are usually due to the compressive effects of the tumor on the neighboring organs. They should be considered in the differential diagnosis of slow-growing benign pancreatic cysts. We describe a 25-year-old woman with a pancreatic teratoma who was operated on in 1976 with the diagnosis of calcified pancreatic cyst. The diagnostic and surgical procedures are described, as well as a 14-year follow-up. The previously published cases are reviewed and the differential diagnosis is discussed. Early diagnosis and the need for total tumor resection are emphasized.

Experimental aspects of elemental diets as radioprotectors

Intensas pesquisas realizadas nas ultimas tres decadas procuraram obter metodos capazes de nutrir adequadamente individuos em situacao normal e apos trauma. A criacao de preparacoes orais sinteticas permitiram avaliar a acao dos varios nutrientes em situacoes especificas, e as assim chamadas dietas elementares se mostraram eficazes. Diversos autores conseguiram produzir enterite actinica tipica, aguda ou cronica, o que permitiu o estudo de substancias radioprotetoras. As dietas elementares tambem foram testadas como "radioprotetores" fisiologicos uma vez que elas poderiam ao mesmo tempo diminuir a lesao intestinal primaria e tratar suas complicacoes. Preparacoes a base de pequenos peptideos, dissacaridios, e acidos graxos de cadeia media conseguiram diminuir a fase aguda em alguns modelos de animais utilizando roedores e caes, e solucoes a base de amino-acidos foram eficazes na prevencao e no tratamento de lesoes cronicas do retossigmoide no rato. Progressos recentes diminuiram a morbidade e mortalidade da fase aguda, mas ainda nao se conseguiram resultados satisfatorios para as lesoes cronicas e irreversiveis. Experimentos em andamento na atualidade vem estudando esta questao, uma vez que as dietas elementares poderao inferir no estabelecimento das sequelas cronicas da radiacao ionizante....