Serosal Adhesion Ex Vivo of Hydrogels Prepared from Apple Pectin Cross-Linked with Fe3+ Ions.

The study aims to investigate the adhesion of a hydrogel made of cross-linked low-methyl esterified pectin to rat intestinal serosa ex vivo. The adhesivity of the FeP hydrogel, which was cross-linked by Fe3+ cations, exceeded that of hydrogels cross-linked by Ca2+, Zn2+, and Al3+ cations. The concentration of the cross-linking cation failed to influence the adhesion of the pectin hydrogel to the serosa. The mechanical properties and surface microrelief of the pectin hydrogel were influenced by the type and concentration of the cross-linking cations. Fe3+ cations form a harder and more elastic gel than Ca2+ cations. Scanning electron microscopy analysis revealed the characteristic surface pattern of FeP hydrogel and its denser internal structure compared to Ca2+ cross-linked hydrogel. The effect of the salt composition of the adhesion medium was shown since the FeP hydrogel's adhesion to the serosa was lower in physiological solutions than in water, and adhesion in Hanks' solution was higher than in phosphate buffered saline. Serum proteins and peritoneal leukocytes did not interfere with the serosal adhesion of the FeP hydrogel. Pre-incubation in Hanks' solution for 24 h significantly reduced the adhesion of the FeP hydrogel to the serosa, regardless of the pH of the incubation. Thus, serosal adhesion combined with excellent stability and mechanical properties in physiological environments appeared to be advantages of the FeP hydrogel, demonstrating it to be a promising bioadhesive for tissue engineering.

Intestine-specific deletion of metal transporter Zip14 (Slc39a14) causes brain manganese overload and locomotor defects of manganism.

Impaired manganese (Mn) homeostasis can result in excess Mn accumulation in specific brain regions and neuropathology. Maintaining Mn homeostasis and detoxification is dependent on effective Mn elimination. Specific metal transporters control Mn homeostasis. Human carriers of mutations in the metal transporter ZIP14 and whole body Zip14-knockout (WB-KO) mice display similar phenotypes, including spontaneous systemic and brain Mn overload and motor dysfunction. Initially, it was believed that Mn accumulation due to ZIP14 mutations was caused by impaired hepatobiliary Mn elimination. However, liver-specific Zip14-KO mice did not show systemic Mn accumulation or motor deficits. ZIP14 is highly expressed in the small intestine and is localized to the basolateral surface of enterocytes. Thus, we hypothesized that basolaterally localized ZIP14 in enterocytes provides another route for the elimination of Mn. Using wild-type and intestine-specific Zip14-KO (I-KO) mice, we have shown that ablation of intestinal Zip14 is sufficient to cause systemic and brain Mn accumulation. The lack of intestinal ZIP14-mediated Mn excretion was compensated for by the hepatobiliary system; however, it was not sufficient to maintain Mn homeostasis. When supplemented with extra dietary Mn, I-KO mice displayed some motor dysfunctions and brain Mn accumulation based on both MRI imaging and chemical analysis, thus demonstrating the importance of intestinal ZIP14 as a route of Mn excretion. A defect in intestinal Zip14 expresssion likely could contribute to the Parkinson-like Mn accumulation of manganism.NEW & NOTEWORTHY Mn-induced parkinsonism is recognized as rising in frequency because of both environmental factors and genetic vulnerability; yet currently, there is no cure. We provide evidence in an integrative animal model that basolaterally localized ZIP14 regulates Mn excretion and detoxification and that deletion of intestinal ZIP14 leads to systemic and brain Mn accumulation, providing robust evidence for the indispensable role of intestinal ZIP14 in Mn excretion.

Development of a risk-scoring system to evaluate the serosal invasion for macroscopic serosal invasion positive gastric cancer patients.

BACKGROUND: The status of serosal invasion is often discordance between pathological and intraoperative evaluation. Our study sought to develop a risk-scoring system (RSS) to predict the probability of pT4a for macroscopic serosal invasion (MSI) positive patients and reevaluate the serosal invasion status. PATIENTS AND METHODS: A total of 1301 pT3/pT4a gastric cancer patients with curative surgery were reviewed. We constructed the RSS to predict the probability of pT4a and assigned MSI-positive patients into different risk groups based on the risk scores. The prognostic significance of these risk groups was also evaluated. RESULTS: Univariate and multivariate analyses identified that tumor location, Lauren type, Borrmann type, tumor size, lymphovascular invasion and pN stage were risk factors related to pT4a. Survival analyses showed that pT3 MSI-positive patients in high-risk group had similar survival with pT4a patients. We incorporated these two groups into one stage and proposed a novel revised-T stage. Two-step multivariate analyses indicated that the revised-T stage showed better prediction ability for prognosis and peritoneal recurrence assessment than original pT stage and MSI status. CONCLUSIONS: In our present study, we developed a RSS to predict the probability of pT4a for MSI-positive patients. Based on our RSS, we proposed a treatment algorithm to reevaluate the tumor invasion for MSI-positive patients in clinical practice. Future studies should include other preoperative predictors to improve the clinical utility of our model.

Tanshinone IIA alleviates lipopolysaccharide-induced acute lung injury by downregulating TRPM7 and pro-inflammatory factors.

The study aimed to investigate the role of Tanshinone IIA (Tan IIA) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in its regulation of TRPM7. Wistar male rats were randomly divided into the normal saline (NS), LPS, knockout (KO) + LPS, low-dose Tan IIA (Tan-L), middle-dose Tan IIA (Tan-M), high-dose Tan IIA (Tan-H) and KO + high-dose Tan IIA (KO + Tan-H) groups. The level of tumour necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, TRPM7 protein expression, current density-voltage curve and Ca2+ concentration were detected through ELISA, Western blotting, electrophysiological experiment and a calcium-imaging technique, respectively. The rats in the KO + LPS, Tan-L, Tan-M, Tan-H and KO + Tan-H groups all displayed lower levels of TNF-α, IL-1ß and IL-6 than the LPS group. Rats in the KO + Tan-H group exhibited lower levels of NF-α, IL-1ß and IL-6 than rats in the Tan-H group. Elevated levels of TRPM7 protein expression in the LPS and Tan groups were detected in comparison with the NS group. However, TRPM7 protein expression in Tan-M and Tan-H groups was notably lower than in that of the LPS group. In comparison with the NS group, the LPS and Tan groups had a greater PIMs cell density and a higher concentration of Ca2+ . Contrary results were observed in the KO + LPS, Tan-H and KO + Tan-H groups. Tan IIA decreases calcium influx in PIMs and inhibits pro-inflammatory factors which provide an alleviatory effect in regards to LPS-induced ALI by suppressing TRPM7 expression.

Effect of a spray formulation on the reproductive parameters of a susceptible population of Rhipicephalus (Boophilus) microplus / Efeitos de uma formulação pulverização sobre os parâmetros reproductivos de uma população susceptível de Rhipicephalus (Boophilus) microplus

The number of studies emphasizing the possible damage that acaricidal spray formulations can cause on engorged female ticks' reproductive parameters is small. The present study evaluated the deleterious effects of a spray formulation (dichlorvos 60% + chlorpyrifos 20%) on the reproductive parameters of a susceptible population of Rhipicephalus (B.) microplus females, using the Stall Test. The ticks were allocated randomly to treatments according to the mean numbers of females detached from each cow on days -3, -2 and -1 and the cattle pen location. The numbers of engorged female ticks that naturally detached from the cattle were counted daily from day 1 to day 30. For each group, 20 detached engorged female ticks or the available number collected daily were evaluated regarding reproductive parameters. Associations of organophosphates demonstrated elevated acaricidal efficacy, as well as deleterious effects on the reproductive parameters of R. (B.) microplus females. The engorged female weight (days 1 to 7), weight of egg masses (days 5 to 10) and larval hatching percentage (days 5 to 19) were decreased (P ≤ 0.05). It is possible that a formulation can lead to deleterious effects on R. (B.) microplus females when the tick population analyzed shows elevated sensitivity towards a particular formulation. However, further studies need to be conducted.

É relativamente pequeno o número de estudos que enfatiza os danos que uma formulação acaricida spray pode desencadear sobre os parâmetros reprodutivos das teleóginas. O presente estudo teve como objetivo avaliar os efeitos deletérios de uma formulação spray comercial (dichlorvos 60% + Clorpirifós 20%), sobre os parâmetros reprodutivos de uma população susceptível de R. (B.) microplus, desprendidas de bovinos experimentalmente infestados, utilizandose o teste de estábulo. Os animais foram alocados aos grupos de tratamentos de acordo com a contagem média de fêmeas desprendidas dos bovinos nos dias -3, -2 e -1. O número de teleóginas desprendidas foi quantificado do dia 1 ao 30. Para cada grupo, diariamente 20 fêmeas, ou a quantidade disponível, foram selecionadas e submetidas à avaliação dos parâmetros reprodutivos. A associação de organofosforados demonstrou elevada eficácia acaricida e também apresentou efeitos deletérios sob os parâmetros reprodutivos de Rhipicephalus (B.) microplus, diminuindo (P≤0,05) o peso das teleóginas (dos dias 1 ao 7), o peso da massa de ovos (dos dias 5 ao 10) e a eclodibilidade das larvas (dos dias 5 ao 19). Talvez uma formulação pode apresentar efeitos deletérios sobre os parâmetros reprodutivos de fêmeas de R. (B.) microplus, quando existe um elevado grau de sensibilidade dessa cepa de carrapato a um determinado composto. De qualquer maneira, futuros estudos devem ser realizados.

Effect of growth hormone, hyperbaric oxygen and combined therapy on the gastric serosa.

AIM: To investigate the role of growth hormone (GH), hyperbaric oxygen therapy (HBOT) and combined therapy on the intestinal neomucosa formation of the gastric serosa. METHODS: Forty-eight male Wistar-albino rats, weighing 250-280 g, were used in this study. The rats were divided into four groups (n = 12): Group 1, control, gastric serosal patch; Group 2, gastric serosal patch + GH; Group 3, gastric serosal patch + HBOT; and Group 4, gastric serosal patch + GH + HBOT. Abdominal access was achieved through a midline incision, and after the 1-cm-long defect was created in the jejunum, a 1 cm × 1 cm patch of the gastric corpus was anastomosed to the jejunal defect. Venous blood samples were taken to determine the insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) basal levels. HBOT was performed in Groups 3 and 4. In Groups 2 and 4, human GH was given subcutaneously at a dose of 2 mg per kg/d for 28 d, beginning on the operation day. All animals were sacrificed 60 d after surgery. The jejunal segment and the gastric anastomotic area were excised for histological examination. The inflammatory process, granulation, collagen deposition and fibroblast activity at the neomucosa formation were studied and scored. Additionally, the villus density, villus height, and crypt depth were counted and recorded. The measurements of villus height and crypt depth were calculated with an ocular micrometer. New vessel growth was determined by calculatingeach new vessel in a 1 mm(2) area. RESULTS: In the histological comparison of groups, no significant differences were observed between the control group and Groups 2 and 3 with respect to epithelialization, granulation, fibroblastic activity and the inflammatory process, but significant differences were present between the control group and all others groups (Groups 2-4) with respect to angiogenesis (P < 0.01) and collagen deposition (P < 0.05, P < 0.01). Significant differences between the control group and Group 4 were also observed with respect to epithelialization and fibroblastic activity (P < 0.01 and P < 0.05, respectively). There were significant differences in villus density in all of groups compared with the control group (P < 0.05). Crypt depth was significantly greater in Group 4 than in the control group (P < 0.05), but no other groups had deeper crypts. However, villus height was significantly longer in Groups 2 and 4 than in the control group (P < 0.05). The comparison of groups revealed, significant difference between control group and Groups 2 and 4) with respect to the levels of IGF-1 and IGFBP-3 (P < 0.01) 3 wk after the operation. CONCLUSION: HBOT or GH and combined therapy augmented on neomucosal formation. The use of combined therapy produced a synergistic effect on the histological, morphological and functional parameters.

Benefits of hyperthermic intraperitoneal chemotherapy for patients with serosal invasion in gastric cancer: a meta-analysis of the randomized controlled trials.

BACKGROUND: In this meta-analysis we aimed to determine the effectiveness and safety of hyperthermic intraperitoneal chemotherapy (HIPC) for patients with advanced gastric cancer who underwent gastrectomy. METHODS: In accordance with standard meta-analysis procedures, our study included patients who underwent resection for advanced gastric cancer and were randomly allocated to receive either hyperthermic intraperitoneal chemotherapy or control. We searched PubMed (up to November 2011), EMBASE (up to November 2011), Cochrane Database of Systematic Reviews (CDSR), and Cochrane Central Register of Controlled Trials (CCTR) (up to November 2011). Both published and unpublished trials were included in the analysis, and no search restrictions were imposed. There was no language restriction. The results were analyzed using RevMan 5.1 software, which was provided by Cochrane Collaboration. RESULTS: There were ten randomized controlled trials included in the analysis. A total of 1062 patients with gastric cancer in these studies were divided into the HIPC group (n = 518) and control group (n = 544). A significant improvement in survival was observed in the HIPC groups compared to the control group in the mitomycin C (MMC) subgroup (RR = 0.75, 95%CI 0.65-0.86; P < 0.00001) and the 5-FU group (RR = 0.69, 95%CI 0.52-0.90; P < 0.00001); the total RR was 0.73 (95%CI 0.64-0.83; P < 0.00001). Our findings indicated that HIPC potentially exhibited a lower peritoneal recurrence rate in the HIPC group compared to the control group (RR = 0.45, 95%CI 0.28-0.72; P = 0.001). CONCLUSIONS: Our meta-analysis demonstrated that HIPC may improve the overall survival rate for patients who receive resection for advance gastric cancer potentially, and help to prevent peritoneal local recurrence among patients with serosal invasion in gastric cancer.

Colon electrical stimulation: potential use for treatment of obesity.

Obesity is one of the most prevalent health problems in the United States. Current therapeutic strategies for the treatment of obesity are unsatisfactory. We hypothesized the use of colon electrical stimulation (CES) to treat obesity by inhibiting upper gastrointestinal motility. In this preliminary study, we aimed at studying the effects of CES on gastric emptying of solid, intestinal motility, and food intake in dogs. Six dogs, equipped with serosal colon electrodes and a jejunal cannula, were randomly assigned to receive sham-CES or CES during the assessment of: (i) gastric emptying of solids, (ii) postprandial intestinal motility, (iii) autonomic functions, and (iv) food intake. We found that (i) CES delayed gastric emptying of solids by 77%. Guanethidine partially blocked the inhibitory effect of CES on solid gastric emptying; (ii) CES significantly reduced intestinal contractility and the effect lasted throughout the recovery period; (iii) CES decreased vagal activity in both fasting and fed states, increased the sympathovagal balance and marginally increased sympathetic activity in the fasting state; (iv) CES resulted in a reduction of 61% in food intake. CES reduces food intake in healthy dogs and the anorexigenic effect may be attributed to its inhibitory effects on gastric emptying and intestinal motility, mediated via the autonomic mechanisms. Further studies are warranted to investigate the therapeutic potential of CES for obesity.

Transepithelial D-glucose and D-fructose transport across the American lobster, Homarus americanus, intestine.

Transepithelial transport of dietary D-glucose and d-fructose was examined in the lobster Homarus americanus intestine using D-[(3)H]glucose and D-[(3)H]fructose. Lobster intestines were mounted in a perfusion chamber to determine transepithelial mucosal to serosal (MS) and serosal to mucosal (SM) transport mechanisms of glucose and fructose. Both MS glucose and fructose transport, as functions of luminal sugar concentration, increased in a hyperbolic manner, suggesting the presence of mucosal transport proteins. Phloridizin inhibited the MS flux of glucose, but not that of fructose, suggesting the presence of a sodium-dependent (SGLT1)-like glucose co-transporter. Immunohistochemical analysis, using a goat anti-rabbit GLUT5 polyclonal antibody, revealed the localization of a brush border GLUT5-like fructose transport protein. MS fructose transport was decreased in the presence of mucosal phloretin in warm spring/summer animals, but the same effect was not observed in cold autumn/winter animals, suggesting a seasonal regulation of sugar transporters. Mucosal phloretin had no effect on MS glucose transport. Both SM glucose and SM fructose transport were decreased in the presence of increasing concentrations of serosal phloretin, providing evidence for the presence of a shared serosal GLUT2 transport protein for the two sugars. The transport of d-glucose and d-fructose across lobster intestine is similar to sugar uptake in mammalian intestine, suggesting evolutionarily conserved absorption processes for these solutes.

Randomized clinical trial of adjuvant chemotherapy with intraperitoneal and intravenous cisplatin followed by oral fluorouracil (UFT) in serosa-positive gastric cancer versus curative resection alone: final results of the Japan Clinical Oncology Group trial JCOG9206-2.

PURPOSE: To evaluate the survival benefit of adjuvant chemotherapy after curative resection in serosa-positive gastric cancer, a multicenter phase III clinical trial was conducted in Japan. PATIENTS AND METHODS: From January 1993 to March 1998, 268 patients were randomized to adjuvant chemotherapy (135 patients) or surgery alone (133 patients). All patients underwent gastrectomy with D2 or greater lymph node dissection. The chemotherapy regimen consisted of intraperitoneal cisplatin soon after abdominal closure, postoperative intravenous cisplatin (day 14) and 5-fluorouracil (day 14-16), and daily oral FU (UFT) starting 4 weeks after surgery for 12 months. The primary endpoint was overall survival. Relapse-free survival and site of recurrence were secondary endpoints. RESULTS: Fifty-two patients (38.5%) in the adjuvant chemotherapy arm completed the chemotherapy regimen. There were 4 (1.49%) treatment-related deaths, 1 in the surgery-alone and 3 in the adjuvant chemotherapy arm (2 did not receive chemotherapy). Grade 4 toxicity was observed in 3 patients in the surgery-alone and 2 patients in the adjuvant chemotherapy arm. There was no significant difference in 5-year overall survival (62.0% adjuvant chemotherapy vs. 60.9% surgery-alone, P = 0.482) and 5-year relapse-free survival rates (57.5% adjuvant chemotherapy vs. 55.6% surgery-alone; P = 0.512). CONCLUSION: There was no benefit in overall and relapse-free survival with this adjuvant chemotherapy regimen for patients with macroscopically serosa-positive gastric cancer after curative resection.

The ACB technique: a biomagentic tool for monitoring gastrointestinal contraction directly from smooth muscle in dogs.

The aim of this paper was to verify whether AC biosusceptometry (ACB) is suitable for monitoring gastrointestinal (GI) contraction directly from smooth muscle in dogs, comparing with electrical recordings simultaneously. All experiments were performed in dogs with magnetic markers implanted under the serosa of the right colon and distal stomach, and their movements were recorded by ACB. Monopolar electrodes were implanted close to the magnetic markers and their electric potentials were recorded by electromyography (EMG). The effects of neostigmine, hyoscine butylbromide and meal on gastric and colonic parameters were studied. The ACB signal from the distal stomach was very similar to EMG; in the colonic recordings, however, within the same low-frequency band, ACB and EMG signals were characterized by simultaneity or a widely changeable frequency profile with time. ACB recordings were capable of demonstrating the changes in gastric and colonic motility determined by pharmacological interventions as well as by feeding. Our results reinforce the importance of evaluating the mechanical and electrical components of motility and show a temporal association between them. ACB and EMG are complementary for studying motility, with special emphasis on the colon. ACB offers an accurate method for monitoring in vivo GI motility.

Absorption of tetraethylammonium (TEA+) by perfused lobster intestine.

The organic cation, tetraethylammonium (TEA(+)), is actively secreted by mammalian nephrons and crustacean urinary bladders by similar processes in both animal groups. These mechanisms consist of a basolateral Organic Cation Transporter (OCT family) that employs the transmembrane electrical potential as a driving force for organic cation uptake from the blood and a brush border secondary active transport process that exchanges luminal protons for TEA(+). The present study examined the nature of (14)C-TEA(+) transport across the perfused intestinal epithelium of the American lobster, Homarus americanus, to ascertain whether the gut complemented the kidneys in the clearance of these organic metabolites from the blood. Unidirectional mucosa to serosa (M to S) (14)C-TEA(+) fluxes in anterior and posterior intestine were hyperbolic functions of luminal [TEA(+)] and significantly (P<0.01) exceeded the respective serosa to mucosa (S to M) fluxes. Luminal quinine (1 mM) significantly (P<0.05) inhibited M to S flux of the organic cation, while serosal addition of the drug had no effect on S to M transfer of TEA(+). Reducing serosal pH from 7.20 to 6.02 significantly (P<0.01) stimulated M to S transfer of 0.1 mM (14)C-TEA(+), but significantly (P<0.05) lowered S to M transfer of the metabolite. Addition of 2.0 mM unlabelled serosal TEA(+) trans-stimulated the M to S flux of 0.1 mM (14)C-TEA and doubled the transfer rate of the organic cation from lumen to blood compared to its transport in the absence of TEA(+) in the bath. Results suggest that this organic cation is absorbed across lobster intestine by the combination of a brush border OCT-1-like transporter coupled with a basolateral H(+)/TEA(+) exchanger. A working model is presented for intestinal organic cation absorption in crustaceans and compared to the secretory transport model for this class of metabolites previously reported for crustacean and mammalian kidneys.

[The effects of desensitization of capsaicin-sensitive neurons on the blood flow in microvessels of the rat gastric serous muscular membrane with normal and insufficient contents of glucocorticoids].

The effects of desensitization of capsaicin-sensitive neurons on the blood flow velocity in microvessels of the gastric muscular membrane were investigated before and after indomethacin (35 mg/kg) administration in adrenalectomized rats with or without corticosterone replacement (4 mg/kg sc) and in sham-operated animals. Desensitization of capsaicin-sensitive neurons was performed with neurotoxic dose of capsaicin (20 + 30 + 50 mg/kg sc) two weeks before the experiment. Adrenalectomy was created one week before the experiment. The in vivo microscopy technique for direct visualization of gastric microcirculation and analysis of red blood cell (RBC) velocity was employed. Indomethacin decreased the RBC velocity. Adrenalectomy by itself profoundly decreased the RBC velocity, whereas corticosterone replacement prevented this effect. Desensitization of capsaicin-sensitive neurons did not influence the RBC velocity in sham-adrenalectomized rats; however, it induced further fall of both basal and indomethacin-induced RBC velocity in adrenalectomized rats that was prevented by corticosterone. We conclude that glucocorticoid hormones have a beneficial effect on the blood flow velocity in microvessels of the gastric muscular membrane in rats with desensitization of capsaicin-sensitive neurons.

[Postoperative adjuvant immunochemotherapy using Lentinan for advanced gastric carcinoma patients with metastasis in the regional lymph nodes and serosal invasion].

Six patients with gastric cancer, stage IIIA to IV, received intraabdominal cisplatin (CDDP) at laporotomy. This was followed by postoperative intravenous infusion of mitomycin C (MMC), CDDP or fluorouracil (5-FU). When these patients recovered to the extent that permitted oral medication, an immunochemotherapeutic regimen containing either oral UFT (uracil and tegafur) or 5'-deoxy-5-fluorouridine (5'-DFUR), plus intravenous Lentinan (LNT) was administered for a period ranging from one and a half to two years. This postoperative immunochemotherapy was successful in all 6 patients. No relapse has been observed in any of them for at least 4 years. These findings indicate that the chemotherapeutic strategy of administering intraabdominal CDDP immediately after surgery, followed by postoperative immunochemotherapy with pyrimidine-fluoride products plus Lentinan on an outpatient basis may be useful in the treatment of T3 or T4 gastric carcinoma with metastasis in the regional lymph nodes.

Postoperative adjuvant chemotherapy is effective in gastric cancer with serosal invasion: significance in patients chosen for multivariate analysis.

There are few reports on overall usefulness of adjuvant chemotherapy in gastric cancer patients. We tried to clarify, using multivariate analysis, usefulness of postoperative adjuvant oral chemotherapy in advanced gastric cancer patients after curative resection. Four hundred and eighty-two gastric cancer patients enrolled in a randomized controlled trial were classified into 2 groups based on postoperative chemotherapeutic regimen: oral doxifluridine (5'-DFUR, an intermediate metabolite of capecitabine) (n=245) or oral 5-fluorouracil (5-FU) (n=237). The significant prognostic factors in patients with serosal invasion were chemotherapeutics (5'-DFUR vs. 5-FU) (risk ratio 1.649; 95% CI, 1.112-2.437), lymph node metastasis (no vs. yes) (2.823; 1.422-5.604), and tumor differentiation (differentiated vs. undifferentiated) (1.727; 1.068-2.791). Significant factors influencing peritoneal recurrence time were chemotherapeutics (1.756; 1.063-2.902), serosal invasion (no vs. yes) (2.237; 1.264-3.961), lymph node metastasis (2.541; 1.267-5.095), tumor differentiation (2.656; 1.374-5.136), and tumor location (others vs. total) (3.595; 2.006-6.443). There were no differences in the overall survival between chemotherapy. However, 5'-DFUR produced a better survival time of patients with serosal invasion than 5-FU, that might be attributed to the prevention of peritoneal recurrence in this subset.

Patrón pronóstico de invasión serosa (S2) en carcinoma gástrico / Prognostic pattern of serous invasion (S2) in gastric carcinoma

El pronóstico del cáncer gástrico depende de la invasión de la pared, compromiso de barreras ganglionares y de factores biológicos tumorales. El objetivo es comunicar nuestra experiencia es un patrón pronóstico asociado a subtipos de compromisos seroso gástrico. Cuarenta y cinco pacientes operados entre 1979 y 1998 cumplen las condiciones de ingreso: carcinoma avanzado, compromiso definitivo de la serosa (S2), gastrectomía total curativa, sin tratamiento complementario. Se establecen dos grupos: Grupo 1 (n:23), con invasión limitada a la membrana serosa. Grupo 2 (n:22), con invasión serosa, rotura y explosión hacia la cavidad peritoneal, pero sin invasión a órganos vecinos. Se analiza características generales y sobrevida según Kaplan-Meier, estimando diferencias con test de Wilcoxon. Las características generales de los grupos 1 y 2 son, respectivamente: Edad promedio: 61-59 años; Sexo (M/F): 16/7-13/9; ubicación tumoral (Zona A/M/C): 3/6/14 - 0/8/14; Clasificación de Bormann (I/II/III/IV): 0/4/810/1 - 0/0/9/9/4. El compromiso de barreras ganglionares (N1/N2): 15/5-13/2. Las principales complicaciones son de causa médica (22,2 por ciento, compartidas por ambos grupos uniformemente. El Grupo 2 tiene dos complicaciones quirúrgicas, tratadas en forma conservadora. Nohay mortalidad en la serie. La sobrevida a 5 años, para el grupo total (n:45) es 33,4 por ciento. La sobrevida del Grupo 1 y 2 es 47,5 por ciento, con diferencia significativa (p=0,05). En esta serie, el compromiso de serosa, abierta ala cavidad peritoneal, se comporta como un factor pronóstico negativo en la sobrevida del cáncer gástrico

Therapeutic Effect of the Intraperitoneal Cisplatin Installation (IPCI) in Advanced Gastric Carcinoma with Serosa Invasion Retrospective study / 대한암학회지

PURPOSE: We performed retrospective study to evaluate the preventive effect of intraperitoneal cisplatin installation (IPCI) on peritoneal recurrence after curative resection of advanced gastric cancer. MATERIALS AND METHODS: The effect of IPCI was evaluated in 297 advanced gastric carcinoma patients from January 1993 to December 1996. In IPCI group, 100 mg/body of cisplatin in one liter of saline was installed in peritoneal cavity before wound closure in operating room and drained out 2 hours later. Postoperative adjuvant chemotherapy with combination of 5-FU and cisplain was performed. 155 cases were treated by IPCI. Median follow-up period was 26 months. RESULTS: Out of 139 (46.8%) recurred cases, peritoneal, local and distant recurrences developed in 65 (37.8%) cases, 66 (38.4%) cases and 41 (23.8%) cases respectively. In univariated analysis for survival and recurrence, IPCI, T stage and N stage were significant prognostic factors. As regards to peritoneal recurrence, IPCI and T stage were significant factors. In multivariated survival analysis, as regards to recurrence, IPCI, T stage and N stage were significant prognostic factors. As regards to peritoneal recurrence, IPCI was the only significant independent prognostic factor. CONCLUSION: We concluded that IPCI can effectively prevent peritoneal recurrence and overall recurrence and it shows marginal survival benefit in advanced gastric cancer patients with serosa invasion.

Peritoneocele. A radiological study with defaeco-peritoneography.

REPORT STUDY: Defaecography reports from 2816 patients were evaluated. Twenty-three percent of the investigations were considered normal, 31% showed rectal intussusception, 13% rectal prolapse, 27% rectocele, and 19% enterocele. A standardised protocol is suggested to ensure a complete evaluation of defaecography. One hundred and ten reports were unclear and reviewed. The unclear reports usually concerned an unexplained widening of the rectovaginal space, and gave incitement to further studies. TECHNIQUE STUDY: Twelve patients with an unexplained widening of the rectovaginal space at defaecography were investigated using defaecography and peritoneography simultaneously, by us named defaeco-peritoneography. All investigations were carried out without complications. Defaeco-peritoneography proved the unexplained widening to be an extension of the pouch of Douglas, a peritoneocele. UNEXPLAINED WIDENING STUDY: Twenty-two patients with unexplained widening of the rectovaginal space noted at defaecography were studied using defaeco-peritoneography. The outline and movements of the peritoneum in the pelvic cavity could be visualised during the dynamic act of defaecation. The unexplained widening of the rectovaginal space was caused completely by a peritoneocele in 14 patients, partially in 6 patients and 2 remained unexplained. However, only 9 out of 22 widenings were peritoneoceles with an enterocele. Just 11 peritoneoceles only contained fluid. Three types of peritoneocele were demonstrated: vaginal, septal, and rectal, with or without enterocele. Combinations of these were also found. RECTAL INTUSSUSCEPTION STUDY: Fifty-seven patients with defaecation disorders were examined using defaeco-peritoneography. Twenty-three patients had rectal intussusception and 7 patients had a rectal prolapse. All these patients had a rectal peritoneocele in the serosal ring-pocket of the rectal intussusception or in the rectal prolapse. Twenty-seven patients had neither rectal intussusception nor rectal prolapse and none of these patients had a rectal peritoneocele. DAILY LIFE STUDY: Twenty-six female patients showing peritoneocele without a contrast-filled rectum at start at defaeco-peritoneography were investigated; 13 of them had enteroceles. Spot radiographs before and after filling the rectum with contrast medium were compared. The peritoneocele disappeared completely in 19 of the patients and was reduced in size in the remaining 7, and the enterocele disappeared completely when the rectum was distended. Defaeco-peritoneography should therefore include a radiograph before the rectum is filled, as it shows the habitual (daily life) anatomy and can disclose pathology as peritoneocele and enterocele. TRANSFORMATION STUDY: Forty-six patients with peritoneocele at defaeco-peritoneography were studied at three different stages during rectal evacuation. At start with contrast-filled rectum, 14 patients had a peritoneocele, and 32 were regarded as normal. At maximum straining, all patients had a peritoneocele and 20 of these were still present after rectal evacuation. The peritoneoceles were largest at straining and rectal types were most common. No enterocele was seen at start. At maximum straining, 21 patients developed an enterocele.

Control of germ-band retraction in Drosophila by the zinc-finger protein HINDSIGHT.

Drosophila embryos lacking hindsight gene function have a normal body plan and undergo normal germ-band extension. However, they fail to retract their germ bands. hindsight encodes a large nuclear protein of 1920 amino acids that contains fourteen C2H2-type zinc fingers, and glutamine-rich and proline-rich domains, suggesting that it functions as a transcription factor. Initial embryonic expression of hindsight RNA and protein occurs in the endoderm (midgut) and extraembryonic membrane (amnioserosa) prior to germ-band extension and continues in these tissues beyond the completion of germ-band retraction. Expression also occurs in the developing tracheal system, central and peripheral nervous systems, and the ureter of the Malpighian tubules. Strikingly, hindsight is not expressed in the epidermal ectoderm which is the tissue that undergoes the cell shape changes and movements during germ-band retraction. The embryonic midgut can be eliminated without affecting germ-band retraction. However, elimination of the amnioserosa results in the failure of germ-band retraction, implicating amnioserosal expression of hindsight as crucial for this process. Ubiquitous expression of hindsight in the early embryo rescues germ-band retraction without producing dominant gain-of-function defects, suggesting that hindsight's role in germ-band retraction is permissive rather than instructive. Previous analyses have shown that hindsight is required for maintenance of the differentiated amnioserosa (Frank, L. C. and Rushlow, C. (1996) Development 122, 1343-1352). Two classes of models are consistent with the present data. First, hindsight's function in germ-band retraction may be limited to maintenance of the amnioserosa which then plays a physical role in the retraction process through contact with cells of the epidermal ectoderm. Second, hindsight might function both to maintain the amnioserosa and to regulate chemical signaling from the amnioserosa to the epidermal ectoderm, thus coordinating the cell shape changes and movements that drive germ-band retraction.

Acute and neonatal capsaicin treatment inhibit jejunal amino acid absorption through a Na+-dependent mechanism.

It has recently been shown that capsaicin inhibits alanine absorption in rat jejunum via mechanisms that involve intestinal capsaicin-sensitive primary afferent (CSPA) fibers. This study provides further evidence that the effect of capsaicin is neurally mediated and demonstrates that CSPA fibers regulate Na+-dependent amino acid absorption. In vivo, basal alanine absorption in rats neonatally treated with capsaicin was reduced by 35% below control. Furthermore, intraluminal perfusion of 400 microM capsaicin reduced jejunal alanine absorption by 31% in sham rats but had no significant effect in rats neonatally treated with capsaicin. In vitro, capsaicin significantly reduced uptake of alanine and proline by jejunal strips but had no effect on uptake of lysine. Tetrodotoxin (0.2 microM) partially blocked the effects of capsaicin but did not itself affect alanine absorption. Capsaicin reduced unidirectional mucosal-to-serosal alanine (1 mM) influx by 33%, an effect that becomes significant after 5 min of preincubation with capsaicin. Neonatal capsaicin treatment reduced basal alanine influx in jejunal strips by 37%; however, preincubation of these strips with capsaicin had no significant effect. Kinetic analysis of alanine steady-state uptake and influx by jejunal strips incubated with capsaicin revealed that capsaicin reduced the Na+-dependent component of alanine influx into intestinal epithelial cells. Long-term sensory denervation by capsaicin also decreased the Na+-dependent component of alanine absorption. These data suggest that intestinal capsaicin-sensitive primary afferent fibers regulate Na+-dependent amino acid absorption.