Early ethanol pre-exposure alters breathing patterns by disruptions in the central respiratory network and serotonergic balance in neonate rats.

Early ethanol exposure alters neonatal breathing plasticity. Respiratory EtOH's effects are attributed to central respiratory network disruptions, particularly in the medullary serotonin (5HT) system. In this study we evaluated the effects of neonatal pre-exposure to low/moderate doses upon breathing rates, activation patterns of brainstem's nuclei and expression of 5HT 2A and 2C receptors. At PD9, breathing frequencies, tidal volumes and apneas were examined in pups pre-exposed to vehicle or ethanol (2.0 g/kg) at PDs 3, 5 and 7. This developmental stage is equivalent to the 3rd human gestational trimester, characterized by increased levels of synaptogenesis. Pups were tested under sobriety or under the state of ethanol intoxication and when subjected to normoxia or hypoxia. Number of c-Fos and 5HT immunolabelled cells and relative mRNA expression of 5HT 2A and 2C receptors were quantified in the brainstem. Under normoxia, ethanol pre-exposed pups exhibited breathing depressions and a high number of apneas. An opposite phenomenon was found in ethanol pre-treated pups tested under hypoxia where an exacerbated hypoxic ventilatory response (HVR) was observed. The breathing depression was associated with an increase in the neural activation levels of the raphe obscurus (ROb) and a high mRNA expression of the 5HT 2A receptor in the brainstem while desactivation of the ROb and high activation levels in the solitary tract nucleus and area postrema were associated to the exacerbated HVR. In summary, early ethanol experience induces respiratory disruptions indicative of sensitization processes. Neuroadaptive changes in central respiratory areas under consideration appear to be strongly associated with changes in their respiratory plasticity.

Brief ethanol exposure and stress-related factors disorganize neonatal breathing plasticity during the brain growth spurt period in the rat.

RATIONALE: The effects of early ethanol exposure upon neonatal respiratory plasticity have received progressive attention given a multifactorial perspective related with sudden infant death syndrome or hypoxia-associated syndromes. The present preclinical study was performed in 3-9-day-old pups, a stage in development characterized by a brain growth spurt that partially overlaps with the 3rd human gestational trimester. METHODS: Breathing frequencies and apneas were examined in pups receiving vehicle or a relatively moderate ethanol dose (2.0 g/kg) utilizing a whole body plethysmograph. The experimental design also considered possible associations between drug administration stress and exteroceptive cues (plethysmographic context or an artificial odor). Ethanol exposure progressively exerted a detrimental effect upon breathing frequencies. A test conducted at PD9 when pups were under the state of sobriety confirmed ethanol's detrimental effects upon respiratory plasticity (breathing depression). RESULTS: Pre-exposure to the drug also resulted in a highly disorganized respiratory response following a hypoxic event, i.e., heightened apneic episodes. Associative processes involving drug administration procedures and placement in the plethysmographic context also affected respiratory plasticity. Pups that experienced intragastric administrations in close temporal contiguity with such a context showed diminished hyperventilation during hypoxia. In a 2nd test conducted at PD9 while pups were intoxicated and undergoing hypoxia, an attenuated hyperventilatory response was observed. In this test, there were also indications that prior ethanol exposure depressed breathing frequencies during hypoxia and a recovery normoxia phase. CONCLUSION: As a whole, the results demonstrated that brief ethanol experience and stress-related factors significantly disorganize respiratory patterns as well as arousal responses linked to hypoxia in neonatal rats.

Prenatal ethanol exposure modifies locomotor activity and induces selective changes in Met-enk expression in adolescent rats.

Several studies suggest that prenatal ethanol exposure (PEE) facilitates ethanol intake. Opioid peptides play a main role in ethanol reinforcement during infancy and adulthood. However, PEE effects upon motor responsiveness elicited by an ethanol challenge and the participation of opioids in these actions remain to be understood. This work assessed the susceptibility of adolescent rats to prenatal and/or postnatal ethanol exposure in terms of behavioral responses, as well as alcohol effects on Met-enk expression in brain areas related to drug reinforcement. Motor parameters (horizontal locomotion, rearings and stereotyped behaviors) in pre- and postnatally ethanol-challenged adolescents were evaluated. Pregnant rats received ethanol (2g/kg) or water during gestational days 17-20. Adolescents at postnatal day 30 (PD30) were tested in a three-trial activity paradigm (habituation, vehicle and drug sessions). Met-enk content was quantitated by radioimmunoassay in several regions: ventral tegmental area [VTA], nucleus accumbens [NAcc], prefrontal cortex [PFC], substantia nigra [SN], caudate-putamen [CP], amygdala, hypothalamus and hippocampus. PEE significantly reduced rearing responses. Ethanol challenge at PD30 decreased horizontal locomotion and showed a tendency to reduce rearings and stereotyped behaviors. PEE increased Met-enk content in the PFC, CP, hypothalamus and hippocampus, but did not alter peptide levels in the amygdala, VTA and NAcc. These findings suggest that PEE selectively modifies behavioral parameters at PD30 and induces specific changes in Met-enk content in regions of the mesocortical and nigrostriatal pathways, the hypothalamus and hippocampus. Prenatal and postnatal ethanol actions on motor activity in adolescents could involve activation of specific neural enkephalinergic pathways.

Conditioned breathing depression during neonatal life as a function of associating ethanol odor and the drug's intoxicating effects.

Fetal and neonatal ethanol-related alterations upon the respiratory system have been described in different mammals. Studies also indicate that perinates learn about the sensory attributes of ethanol and associate them with diverse physiological effects of the state of intoxication. The present study was conducted in rat neonates during a developmental stage equivalent to the third human gestational trimester. The major goal was to analyze the consequences of ethanol odor exposure, the state of intoxication, or the temporal contiguity between these factors upon breathing patterns. The main findings were as follows: (a) a conditioned breathing depression was observed following few trials defined by the association between ethanol odor and the state of intoxication and (b) sequential exposure to ethanol sensitizes the organism to the drug's respiratory depressant effects without affecting ethanol metabolism. These results indicate that early breathing disruptions caused by ethanol can be determined or modulated via learning processes. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:670-686, 2016.

Prenatal binge-like alcohol exposure alters brain and systemic responses to reach sodium and water balance.

The aim of the present work is to analyze how prenatal binge-like ethanol exposure to a moderate dose (2.0 g/kg; group Pre-EtOH) during gestational days (GD) 17-20 affects hydroelectrolyte regulatory responses. This type of exposure has been observed to increase ethanol consumption during adolescence (postnatal day 30-32). In this study we analyzed basal brain neural activity and basal-induced sodium appetite (SA) and renal response stimulated by sodium depletion (SD) as well as voluntary ethanol consumption as a function of vehicle or ethanol during late pregnancy. In adolescent offspring, SD was induced by furosemide and a low-sodium diet treatment (FURO+LSD). Other animals were analyzed in terms of immunohistochemical detection of Fra-like (Fra-LI-ir) protein and serotonin (5HT) and/or vasopressin (AVP). The Pre-EtOH group exhibited heightened voluntary ethanol intake and a reduction in sodium and water intake induced by SD relative to controls. Basal Na and K concentrations in urine were also reduced in Pre-EtOH animals while the induced renal response after FURO treatment was similar across prenatal treatments. However, the correlation between urine volume and water intake induced by FURO significantly varied across these treatments. At the brain level of analysis, the number of basal Fra-LI-ir was significantly increased in AVP magnocellular neurons of the paraventricular nucleus (PVN) and in 5HT neurons in the dorsal raphe nucleus (DRN) in Pre-EtOH pups. In the experimental group, we also observed a significant increase in Fra-LI along the nucleus of the solitary tract (NTS) and in the central extended amygdala nuclei. In summary, moderate Pre-EtOH exposure produces long-lasting changes in brain organization, affecting basal activity of central extended amygdala nuclei, AVP neurons and the inhibitory areas of SA such as the NTS and the 5HT-DRN. These changes possibly modulate the above described variations in basal-induced drinking behaviors and renal regulatory responses.

Prenatal ethanol exposure alters met-enkephalin expression in brain regions related with reinforcement: possible mechanism for ethanol consumption in offspring.

The endogenous opioid system is involved in ethanol reinforcement. Ethanol-induced changes in opioidergic transmission have been extensively studied in adult organisms. However, the impact of ethanol exposure at low or moderate doses during early ontogeny has been barely explored. We investigated the effect of prenatal ethanol exposure on alcohol intake and Methionine-enkephalin (Met-enk) content in rat offspring. Met-enk content was assessed in the ventral tegmental area [VTA], nucleus accumbens [NAcc], prefrontal cortex [PFC], substantia nigra [SN], caudate-putamen [CP], amygdala, hypothalamus and hippocampus. Pregnant rats were treated with ethanol (2g/kg) or water during GDs 17-20. At PDs 14 and 15, preweanlings were evaluated in an intake test (5% and 10% ethanol, or water). Met-enk content in brain regions of infants prenatally exposed to ethanol was quantitated by radioimmunoassay. Ethanol consumption was facilitated by prenatal experience with the drug, particularly in females. Met-enk content in mesocorticolimbic regions - PFC and NAcc - was increased as a consequence of prenatal exposure to ethanol. Conversely, Met-enk levels in the VTA were reduced by prenatal ethanol manipulation. Prenatal ethanol also increased peptide levels in the medial-posterior zone of the CP, and strongly augmented Met-enk content in the hippocampus and hypothalamus. These findings show that prenatal ethanol exposure stimulates consumption of the drug in infant rats, and induces selective changes in Met-enk levels in regions of the mesocorticolimbic and nigrostriatal systems, the hypothalamus and hippocampus. Our results support the role of mesocorticolimbic enkephalins in ethanol reinforcement in offspring, as has been reported in adults.

Acetaldehyde involvement in ethanol's postabsortive effects during early ontogeny.

Clinical and biomedical studies sustains the notion that early ontogeny is a vulnerable window to the impact of alcohol. Experiences with the drug during these stages increase latter disposition to prefer, use or abuse ethanol. This period of enhanced sensitivity to ethanol is accompanied by a high rate of activity in the central catalase system, which metabolizes ethanol in the brain. Acetaldehyde (ACD), the first oxidation product of ethanol, has been found to share many neurobehavioral effects with the drug. Cumulative evidence supports this notion in models employing adults. Nevertheless very few studies have been conducted to analyze the role of ACD in ethanol postabsorptive effects, in newborns or infant rats. In this work we review recent experimental literature that syndicates ACD as a mediator agent of reinforcing aspects of ethanol, during early ontogenetic stages. We also show a meta-analytical correlational approach that proposes how differences in the activity of brain catalase across ontogeny, could be modulating patterns of ethanol consumption.

CD133 is a selective marker of CRC?

AIM: The aim of our study is to evaluate the surface glycoprotein CD133 as marker of cancer stem cells, as independent prognostic pattern of survival and its positive expression ratio to a chemotherapy increased resistance. METHODS: The study include our patient, affected by colorectal cancer (CRC) and underwent to surgery at University Hospital of Parma, with curative intent, with a follow up of 5 years; 47 cases were considered. All the cancer-case was considered independently by the histological grade. The monoclonal antibody CD133/1 (clone AC133-MAC, Miltenyi Bioetec, Auburn CA 95602, USA) that recognizes the epitope 1 of CD133 was utilized for the immunohistochemical process. RESULTS: On the total of 47 patients taken in exam, 8 were excluded for lack of date, 13 were lost during the follow-up. The final number of patients included in the study was 26(17 males and 9 females), medium age of 72.2 years. 2 Stage I, 8 Stage II A, 1 II B, 2 III A, 5 III B, 5 IIIC and 3 IV. Despite for 1, 25 on 26 patients were positive to CD133 (96.5 %), with different dye intensity, directly related at the positive cell pull. The CD133 positivity wasn't therefore related at any other clinic-pathological characteristic. CONCLUSION: The results obtained from our study goes in the same direction with others, that confirm a high representation of CD133 on the colic tumoral epithelium. It will be appropriate to do prospected and randomized studies, with a larger casistic, utilizing similar methods and a patients populations with more uniform characteristics, to verify the real role of CD133 and other molecules potentially marker of tumoral stem cell (TSC).

Use of preoperative visceral echo-color-Doppler in patients candidates to colonic surgery: preliminary report.

AIM: Postsurgical paralytic ileus is by definition an ileal paralysis longer than three days (72 hours) after a surgery on the gastrointestinal tract. At colorectal surgery we have performed on all candidates a visceral echo-color-Doppler to find a potential correlation with cardiovascular risk factors. METHODS: We have tested patients undergone to colorectal surgical resection performed by laparoscopic and laparotomic surgery, looking for their atherosclerosis status using ultrasound scan, postsurgical complication, bowel digestive function, anastomotic leak. We have also analyzed for each case the value of glycemia, azotemia, creatinemia, cholesterolemia, triglyceridemia, leukocytemia, mean cell volume, hemoglobinemia, albuminemia and moreover age, disease, pathology localization, kind of surgery, weight and height, body mass index (BMI), ASA status (American Society of Anesthesiologists, electrocardiographic distortions, nicotine dependency, diabetes mellitus type I and II). RESULTS: The study enrolled 23 patients, 10 male and 13 female. Middle age was 68.65 ± 11.85 years (range 39-90). In the female subgroup mean age was 69.48 years (range 39-90), while in the male subgroup it was 68 years (range 54-81). In 17 cases out of 23 (73.9%) there was a delay in digestive function, of over 72 hours, with a mean time duration of the paralytic ileus of 4.74 ± 1.60 days (range 3-9). Furthermore a statistically significant correlation between albuminemia and hemoglobinemia presurgery values and lower sierical albuminemia presurgery values in patients who were canalized too late (P=0.03; P=0.041) was found. The non-parametrical values analysis sec. Kruskal-Wallis emphasized a significant correlation between the canalization day, the elettrocardiographic evidence of the pathological situation (P=0.023) and the patient's smoking history (0.023). Another significant value was the creatininemia value: lower values of creatininemia were related to a delayed canalization (P=0.035). CONCLUSION: The statistical analysis does not allow to highlight any correlation between the ultrasound diagnosis of atherosclerosis and the delayed canalization.

Right colon laparoscopic resection with three-trocar access and associated gynecological procedures in patients with colorectal cancer and ovarian metastases.

BACKGROUND: Right laparoscopic colectomy was introduced to colorectal surgery later than the left colon procedure. Three-trocar laparoscopy has already been used successfully in the treatment of gynecological cancers. In the present study, we aimed to analyze the feasibility of performing an associated gynecological procedure following abdominal laparoscopic exploration and to evaluate the suitability of laparoscopic right colectomy for treating elderly patients. METHODS: We conducted a review of prospectively collected data on 100 consecutive patients who were treated with right laparoscopic colectomy using three trocars from January 2005 to April 2010. We recorded the patients' age (<70 or > 70 years), ASA status, body mass index (BMI), pain on postoperative days 1 and 2 (POD 1, 2), nodes retrieved, laparotomic conversion, mean operative time, time to intestinal recovery, and length of postoperative stay. RESULTS: All subjects were treated for cancer. Conversion to the laparotomic procedure was performed in 13/100, with no difference in terms of age. Operative time was longer for laparotomic conversion (p <0.05), with a longer postoperative stay. Elderly patients had higher ASA scores (p < 0.005); age did not influence the conversion rate or BMI status. Pain on POD 1 and 2 differed between the laparotomic and laparoscopic groups (p <0.0001). Associated procedures were performed in five subjects (3 oophorectomy and 2 cholecystectomy). CONCLUSIONS: Laparoscopy using the three-trocar technique is a safe procedure for treating colon cancer, including in elderly patients, and enables associated gynecological laparoscopic procedures to be performed.

Laparoscopic treatment of sigmoid colon intussusception by large malignant tumor. Case report.

Intestinal intussusception is rare in adults, but common in children. The ileocolic or appendiceal types are more frequent compared to the colo-colic one. We report successful laparoscopic left hemicolectomy in a patient with intussusception caused by a sigmoid tumor. Abdominal CT demonstrated a colo-colic intussusception at the level of the tumoral lesion with dilation of the proximal colon. The patient underwent urgent laparoscopic oncologically radical left hemicolectomy. A 10 cm Pfannenstiel incision allowed the removal of the resected segment. The laparoscopic approach was feasible because the dilation was moderate; however, if intussusception is due to cancer, laparoscopy can be safely performed if a correct and prompt diagnosis is achieved following oncologic criteria.

Complications of percutaneous endoscopic gastrostomy: a surgical experience.

AIM: Percutaneous endoscopic gastrostomy (PEG) is a practical and safe option to place an alimentary gastrostomy. We observed that a relevant rate of complications are related to management of PEG. PATIENTS AND METHODS: We registered the patients treated in our Unit from September 1994 to December 2005. We placed 293 PEG (243 pts). Preferably using a tube 16 Fr, in 7 cases 18 Fr, in 21 cases 20 Fr and only in 3 cases 9 Fr. The median age was 69.8 years; ratio female:male 3:1. In 67 cases the treatment was carried out in not hospitalized patients. RESULTS: The incidence of late and early complications is statistically higher in hospitalized patients than at home. CONCLUSION: We think that a correct management of PEG (nurses correct information) and the experience of endoscopist and a dietician can significantly reduce the rate of complications.

Standardized laparoscopic right hemicolectomy technique for colon cancer.

AIM: We analysed our experience of laparoscopic surgical treatment vs traditional surgery of right colon cancer. METHODS: A series of 27 patients was treated from January 2001 to December 2005 out of a total of 927 surgical colorectal operations in the same period (147 with the laparoscopic approach). Inclusion and exclusion criteria are reported. We compared this group with 25 patients treated by the same surgical group with open surgery. The mean operative time, the distance from the distal margin of resection, the number of lymphnodes, the mean period of canalization and the mean hospital stay are reported. RESULTS: In the laparoscopic group, the mean operative time was 124.8+/-36.3 min vs open surgery group of 94+/-23.6 min; the distance from the distal margin was 6.7+/-3.1 cm vs 6.4+/-2.1 cm; number of lymphnodes was 15.2+/-4.3 vs 18.7+/-2.9 nodes; and canalization 1.7+/-0.9 vs 2.7+/-0.7 days. The hospital stay was 6.8+/-1.7 vs 7.2+/-0.8 days. CONCLUSIONS: We consider laparoscopic right colon resection a safe procedure but it needs good laparoscopic practice and the observance of inclusion criteria.

[Longo hemorrhoidopexy vs Milligan-Morgan hemorrhoidectomy: perspective analysis]. / Emorroidopessi secondo Longo versus emorroidectomia secondo Milligan-Morgan: analisi prospettica.

The authors analyzed their experience from January 2001 to February 2005 on 117 patients treated with Longo hemorrhoidopexy (46 cases) and Milligan-Morgan hemorroidectomy (71 cases). All the patients were observed after a week and one month after surgical procedure; at 6 months the Authors controlled 70 patients treated with Milligan-Morgan and 33 treated with Longo technique. The pain after 24 hours was the same in two groups but after a week a significative difference between two groups (p<0.05) was registered with a better quality of life for hemorrhoidopexy group. At 6 months pain during defecation was present in two cases of Longo group and in 6 cases of Milligan-Morgan group. In author's experience the Longo technique is a safe treatment with lower postsurgical pain and lower complications.

[Laparoscopic colectomy in the treatment of colon cancer: prospective study]. / La colectomia laparoscopica nel trattamento del carcinoma del colon: studio prospettico.

The Authors report their experience on laparoscopic colectomy in 38 patients treated between June 2001-September 2003 in General Surgery and Organ Transplantation Department of University of Parma, Italy. The patients were 23 male and 15 female, with average age 58.4 years. All patients were studied with TC and colonoscopy performed by the surgeon. The conversion rate was 15.8% and the average hospital stay 6.9 days (range 6-15 days). The patient's general clinical conditions and the results showed that the laparoscopic colectomy is a safe surgical option.

The size of pancreatic pseudocyst does not influence the outcome of invasive treatments.

BACKGROUND: Authors generally agree that Giant Pancreatic Pseudocysts (> 10 cm) have a lower spontaneous resolution and are more difficult to treat than smaller pancreatic pseudocysts. This study was carried out on two groups of patients with larger and smaller pancreatic pseudocysts (pancreatic pseudocysts > 10 cm versus pancreatic pseudocysts < 10 cm), and aims to establish whether the size of pancreatic pseudocysts is a factor influencing treatment outcomes. PATIENTS AND METHODS: In a retrospective study, we examined 71 patients with pancreatic pseudocysts following an episode of acute pancreatitis, which were treated in our hospital from 1980 to 2000. Forty-one (57.5%) patients had a large pancreatic pseudocyst. Most patients underwent invasive treatments: 9 (12.6%) had percutaneous drainage, 37 (52.1%) open surgery and 13 (18.3%) endoscopic cyst gastrostomy. 12 patients (16.9%) of the 71 were cured with medical therapy alone. RESULTS: As far as the aetiology of the pancreatitis, location and number of the cysts were concerned, no major differences emerged between the two groups, although large pancreatic pseudocysts followed more severe pancreatitis (P = 0.0005). All giant pancreatic pseudocysts required invasive treatments; 40% of the pancreatic pseudocysts < 10 cm were successfully treated with medical therapy alone. No statistical differences were found regarding hospital mortality, morbidity, recurrence rate and hospital stay among the patients treated invasively. CONCLUSIONS: Giant pancreatic pseudocysts more often require invasive therapy due to persistent symptoms or complications. Treatment outcomes do not seem to be influenced by the size of the pancreatic pseudocysts.

Laparoscopic technique in enlarged cystic duct.

The risk of dislodgment of endoclips placed during laparoscopic cholecystectomy in enlarged cystic duct is higher with minor bile leak. From January 2000 to April 2004, we performed 1013 procedures; in 12 patients we have showed a enlarged duct ligated with 4 laparoscopic cholecystectomy endoclips after a 180 degrees rotation of the gallbladder during a retrograde cholecystectomy. We haven't registered complications and all the cases were discharged the first postoperative day. The method is safe and economically sound.