Salivary Sex Steroid Levels in Infants and the Relation with Infantile Colic

Objective: The hypothalamic-pituitary-gonadal axis is active during minipuberty, the timing of which coincides with infantile colic. To the best of our knowledge, the relationship between these entities has not been previously investigated. Methods: Saliva samples were collected from 15- to 60-day-old term infants (n=139) between 9 am and 5 pm. Group 1 included infants with infantile colic (n=68, 54.4% female) while the remaining healthy infants constituted Group 2 (n=71, 47.9% female). Salivary levels of estradiol (Esal) in females and testosterone (Tsal) in males were measured by ELISA in duplicate. Results: The median (25th-75th centile) age and birth week for all infants were 33 (29-43) days and 39 (38.1-40) weeks, respectively. Levels of Tsal in males [Group 1, 73.35 (59.94-117.82) pg/mL vs Group 2, 77.66 (56.49-110.08) pg/mL, p=0.956] and Esal in females [Group 1, 3.91 (2.76-5.31) pg/mL vs Group 2, 4.03 (1.63-12.1) pg/mL, p=0.683] were similar. However, in subjects with infantile colic (Group 1), Esal and body mass index (BMI) standard deviation scores of females were slightly correlated (Group 1, rs= 0.393, p=0.016 vs. Group 2, rs= 0.308, p=0.076) and there was a significant correlation between the sampling time and Tsal in males (Group 1, rs= 0.469, p=0.009 vs. Group 2, rs= -0.005, p=0.976). Conclusion: Random salivary sex steroid levels were similar in infants with and without infantile colic. However, in subjects with infantile colic, Esal levels in females were positively correlated with BMI and Tsal levels were higher later in the day among males. Thus, sex steroid production may be altered during minipuberty in subjects with infantile colic.

The Role of Breast Milk Neurotrophin Levels in Infantile Colic Pathogenesis: A Cross-Sectional Case-Control Study.

Objective: Immaturity of the digestive tract and enteric nervous system is a widely accepted theory for infantile colic (IC) etiopathogenesis. The study aimed to show whether neurotrophins that are necessary for normal functioning and development of the gastrointestinal system have a role in the pathogenesis of IC. Materials and Methods: The IC group (n = 75) comprising the mothers of infants with IC and the control group (n = 75) were included to this cross-sectional case-control study. Brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), and nerve growth factor (NGF) levels of breast milk samples were evaluated by immunosorbent analysis method. Results: The mean age of infants with IC was 7.3 ± 2.8 weeks, while the mean age of the control group was 8.1 ± 2.9 weeks (p = 0.110). No significant difference was found between the breast milk BDNF, GDNF, CNTF, and NGF levels of two groups (p = 0.941, p = 0.510, p = 0.533, p = 0.839, respectively). Conclusions: This is the first report comparing the neurotrophin levels of the breast milk samples taken from the mothers of infants with and without IC. The study demonstrated that breast milk neurotrophin levels of the mothers did not differ significantly between the infants with and without IC.

The In Vitro Digestion and Fermentation Characteristics of Feedstuffs Inoculated With Cecal or Colic Fluid of Dezhou Donkey.

The present study was conducted to evaluate the in vitro dry matter disappearance (IVDMD) and fermentation characteristics of 6 fibrous feedstuffs incubated with donkey cecal or colic microorganisms. The fibrous feeds were corn straw, wheat straw, peanut vine, peanut shell, wheat shell and wheat bran (WB), which are commonly applied in large-scale donkey farms in China. After 48 hours fermentation, the highest IVDMD occurred in WB, and the lowest occurred in peanut shell (P < .05) regardless what inoculum applied. The IVDMD was positively correlated with OM (R = 0.42, P < .01), CP (R = 0.76, P < .01) and EE (R = 0.56, P < .01), while it was negatively correlated with NDF (R = 0.75, P < .01) and ADF (R = 0.79, P < .01). In terms of volatile fatty acids (VFAs), the greatest net VFA production also occurred in WB (P < .05). The acetate and branched-chain volatile fatty acid proportions were greater in the colon culture fluids than in caecum (P < .05), but the propionate proportions were lower in colon than in caecum (P < .05). This resulted in an increase in the ratio of acetate to propionate in colon culture fluids. In summary, based on the highest IVDMD, net VFA production and CP content occurring with the lowest contents of both NDF and ADF, WB had the highest nutritive value compared to other fibrous substrates. The extent of feed degradation and fermentation depended mainly on the nature of the incubated feedstuffs. Nevertheless, further study is required to investigate these fibrous feeds on hindgut fermentation and in vivo nutrient digestibility.

MMP-9 Concentration in Peritoneal Fluid Is a Valuable Biomarker Associated with Endotoxemia in Equine Colic.

The purpose of the study was to compare the results of sepsis scoring (clinical examination and clinical pathology) to the concentrations of matrix-metalloproteinases (MMPs) -2, -8, and -9; tissue-inhibitor of metalloproteinases (TIMPs) -1 and -2; and inflammatory chemokines interleukin (IL) 1ß and tumor-necrosis-factor-alpha (TNF-α) in plasma and peritoneal fluid of equine colic patients. A modified sepsis scoring including general condition, heart and respiratory rate, rectal temperature, mucous membranes, white blood cell count (WBC), and ionized calcium was applied in 47 horses presented with clinical signs of colic. Using this scoring system, horses were classified as negative (n = 32, ≤6/19 points), questionable (n = 9, 7-9/19 points), or positive (n = 6, ≥10/19 points) for sepsis. MMPs, TIMPs, IL-1ß, and TNF-α concentrations were evaluated in plasma and peritoneal fluid using species-specific sandwich ELISA kits. In a linear discriminant analysis, all parameters of sepsis scoring apart from calcium separated well between sepsis severity groups (P < 0.05). MMP-9 was the only biomarker of high diagnostic value, while all others remained insignificant. A significant influence of overall sepsis scoring on MMP-9 was found for peritoneal fluid (P = 0.005) with a regression coefficient of 0.092, while no association was found for plasma (P = 0.085). Using a MMP-9 concentration of >113 ng/ml in the peritoneal fluid was found to be the ideal cutoff to identify positive sepsis scoring (≥10/19 points; sensitivity of 83.3% and specificity of 82.9%). In conclusion, MMP-9 was found to be a biomarker of high diagnostic value for sepsis and endotoxemia in equine colic. The evaluation of peritoneal fluid seems preferable in comparison to plasma. As abdominocentesis is commonly performed in the diagnostic work-up of equine colic, a pen-side assay would be useful and easy-to-perform diagnostic support in the decision for therapeutic intervention.

Microvesicles from Lactobacillus reuteri (DSM-17938) completely reproduce modulation of gut motility by bacteria in mice.

Microvesicles are small lipid, bilayer structures (20-400 nm in diameter) secreted by bacteria, fungi, archaea and parasites involved in inter-bacterial communication and host-pathogen interactions. Lactobacillus reuteri DSM-17938 (DSM) has been shown to have clinical efficacy in the treatment of infantile colic, diarrhea and constipation. We have shown previously that luminal administration to the mouse gut promotes reduction of jejunal motility but increases that in the colon. The production of microvesicles by DSM has been characterized, but the effect of these microvesicles on gastrointestinal motility has yet to be evaluated. To investigate a potential mechanism for the effects of DSM on the intestine, the bacteria and its products have here been tested for changes in velocity, frequency, and amplitude of contractions in intact segments of jejunum and colon excised from mice. The effect of the parent bacteria (DSM) was compared to the conditioned media in which it was grown, and the microvesicles it produced. The media used to culture the bacteria (broth) was tested as a negative control and the conditioned medium was tested after the microvesicles had been removed. DSM, conditioned medium, and the microvesicles all produced comparable effects in both the jejunum and the colon. The treatments individually decreased the velocity and frequency of propagating contractile cluster contractions in the jejunum and increased them in the colon to a similar degree. The broth control had little effect in both tissues. Removal of the microvesicles from the conditioned medium almost completely eradicated their effect on motility in both tissues. These results show that the microvesicles from DSM alone can completely reproduce the effects of the whole bacteria on gut motility. Furthermore, they suggest a new approach to the formulation of orally active bacterial therapeutics and offer a novel way to begin to identify the active bacterial components.

Salivary alpha-amylase activity and cortisol in horses with acute abdominal disease: a pilot study.

BACKGROUND: The aim of this study was to evaluate salivary alpha-amylase (sAA), considered a non-invasive biomarker for sympathetic nervous system (SNS) activity, and salivary cortisol as possible pain-induced stress biomarker, in horses with acute abdominal disease. Therefore, a prospective observational study was performed in which both biomarkers were analyzed in a group of horses with acute abdomen syndrome, and compared with a group of healthy control horses by an unpaired Student's t-test. In addition, the possible relationship between both biomarkers, the score in Equine Acute Abdominal Pain scales version 1 (EAAPS-1 scale), Heart Rate (HR) and Respiratory Rate (RR), plasma lactate, the systemic inflammatory response syndrome (SIRS) score and serum amyloid A (SAA) concentration was assessed by a Spearman correlation test. RESULTS: A total of 30 horses were included in the study, 19 with acute abdominal disease diagnosed as large colon displacements, simple impactions of the pelvic flexure, spasmodic colics and enteritis and 11 healthy ones. sAA activity (24.5 median-fold, P <  0.0001) and salivary cortisol (1.7 median-fold, P <  0.01) were significantly higher in horses with acute abdomen than in healthy horses. sAA activity was significantly correlated with EAAPS-1 scale (r = 0.78, 95% confidence interval [CI] 0.38-0.89, P < 0.001) and SIRS score (r = 0.49, 95% CI 0.03-0.78, P < 0.05). Neither sAA nor salivary cortisol correlated with HR, RR, plasma lactate and SAA. CONCLUSIONS: Although this study should be considered as preliminary one, alpha-amylase measurements in saliva could be a biomarker of pain-induced stress in horses with acute abdominal disease.

The role of melatonin and cortisol circadian rhythms in the pathogenesis of infantile colic.

BACKGROUND: Despite the high prevalence of infantile colic, the pathogenesis remains incompletely understood. Cortisol and melatonin hormones affect gastrointestinal system development in several ways, and interestingly, both cortisol and melatonin's circadian rhythms begin around the 3rd month in which infantile colic symptoms start to decrease. We hypothesized that infantile colic might associate with desynchronization of normal circadian rhythms of these hormones. In this study, we aimed to investigate the role of melatonin and cortisol in the pathogenesis of infantile colic. METHODS: Patients who were diagnosed as infantile colic according to Wessel's "rule of three" were enrolled in the colic group. We measured the saliva melatonin and cortisol levels of colic group and control group infants. In both groups, the saliva samples were taken in mornings and at evenings, at the time of diagnosis and 6th month. RESULTS: Fifty-five infants finished the study. Melatonin circadian rhythm developed earlier in the control group than the infantile colic group in our study. We found no significant difference between the daily mean cortisol levels. However, infants with colic had flatter daily cortisol slope than controls which pointed out the probability that they had a less clearly defined cortisol rhythm than infants without colic. CONCLUSIONS: We found an association between melatonin levels and infantile colic. However, more research is needed to fully understand the role of hypothalamic-pituitary-adrenal axis and hormone's role on infantile colic physiopathology.

Crying Time and RORγ/FOXP3 Expression in Lactobacillus reuteri DSM17938-Treated Infants with Colic: A Randomized Trial.

OBJECTIVES: To evaluate crying time, retinoid-related orphan receptor-γ (RORγ) and forkhead box P3 (FOXP3) messenger RNA levels (transcription factors that can modulate T cell responses to gut microbes), and to investigate gut microbiota and fecal calprotectin in infants treated with Lactobacillus reuteri for infantile colic. STUDY DESIGN: A double-blind, placebo-controlled randomized trial was conducted in primary care in Torino from August 1, 2015 to September 30, 2016. Patients suffering from infantile colic were randomly assigned to receive daily oral L reuteri (1 × 108 colony forming unit) or placebo for 1 month. Daily crying times were recorded in a structured diary. FOXP3 and RORγ messenger RNA in the peripheral blood was assessed with real-time TaqMan reverse transcription polymerase chain reaction. Gut microbiota and fecal calprotectin were evaluated. RESULTS: After infants with colic were supplemented with L reuteri DSM 17938 for 30 days, crying times were significantly shorter among infants with colic in the probiotic group compared with infants in the placebo group (74.67 ± 25.04 [IQR = 79] minutes /day vs 147.85 [IQR = 135] minutes /day [P = .001]). The FOXP3 concentration increased significantly (P = .009), resulting in decreased RORγ/FOXP3 ratios: 0.61 (IQR = 0.60) at day 0 and 0.48 (IQR = 0.28) at day 30 (P = .028). Furthermore, the probiotic increased the percentage of Lactobacillus (P = .049) and decreased fecal calprotectin (P = .0001). CONCLUSIONS: Infants with colic treated with L reuteri for 30 days had a significantly decreased crying time and an increased FOXP3 concentration, resulting in a decreased RORγ/FOXP3 ratio. The treatment reduced fecal calprotectin. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00893711.

Lactobacillus reuteri for Infants with Colic: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

OBJECTIVE: To assess the safety of probiotic Lactobacillus reuteri strain Deutsche Sammlung von Mikroorganismen (DSM) 17938 with daily administration to healthy infants with colic and to determine the effect of L reuteri strain DSM 17938 on crying, fussing, inflammatory, immune, and microbiome variables. STUDY DESIGN: We performed a controlled, double-blinded, phase 1 safety and tolerability trial in healthy breast-fed infants with colic, aged 3 weeks to 3 months, randomly assigned to L reuteri strain DSM 17938 (5 × 108 colony-forming units daily) or placebo for 42 days and followed for 134 days. RESULTS: Of 117 screened infants, 20 were randomized to L reuteri strain DSM 17938 or placebo (sunflower oil) (in a 2:1 ratio) with 80% retention. Eleven of the 20 (55%) presented with low absolute neutrophil counts (<1500/mm3), which resolved in all subjects by day 176. L reuteri strain DSM 17938 produced no severe adverse events and did not significantly change crying time, plasma bicarbonate, or inflammatory biomarkers. Fecal calprotectin decreased rapidly in both groups. In the infants with dominant fecal gram negatives (Klebsiella, Proteus, and Veillonella), resolution of colic was associated with marked decreases in these organisms. CONCLUSIONS: Daily administration of L reuteri strain DSM 17938 appears to be safe in newborn infants with colic, including those with neutropenia, which frequently coexists. A placebo response of 66% suggests that many infants with colic will have resolution within 3 weeks. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01849991.

Plasma HMGB-1 and Nucleosome Concentrations in Horses with Colic and Healthy Horses.

BACKGROUND: Acute gastrointestinal disease occurs commonly in horses. Novel biomarkers might improve the understanding of SIRS and aid diagnosis and determination of prognosis. HYPOTHESES: Increased plasma concentrations of the biomarkers HMGB-1 and nucleosomes are associated with severity of gastrointestinal lesions in horses; concentrations of these biomarkers will be greater in horses with lesions more likely to cause SIRS; and will provide additional information compared with standard biomarkers fibrinogen and SAA. ANIMALS: Thirty horses with gastrointestinal disease, 22 healthy horses. METHODS: Prospective study. Plasma samples taken on admission were used for measurement of HMGB-1, nucleosomes, fibrinogen, and SAA. Values were compared between healthy horses and those with gastrointestinal disease, and between horses with gastrointestinal disease grouped by lesion type (inflammatory, strangulating, and nonstrangulating). Correlations between biomarkers were assessed. RESULTS: Plasma concentrations of all biomarkers were significantly higher in horses with gastrointestinal disease compared to healthy horses (P ≤ .001). HMGB-1 and nucleosomes were significantly higher in inflammatory and strangulating groups compared to healthy horses (3.5-fold and 5.4-fold increases, respectively, for HMGB-1 (P < .05) and 4.8-fold and 5.6-fold increases for nucleosomes (P < .05)), but concentrations in the group with nonstrangulating disease did not differ from healthy horses. There was significant correlation between HMGB-1 and nucleosomes (Spearman's r = 0.623; P < .001), and fibrinogen and SAA (Spearman's r = 0.801; P < .001) but not between other biomarkers. CONCLUSIONS AND CLINICAL IMPORTANCE: High mobility group box-1 and nucleosomes might have use as biomarkers for horses with gastrointestinal disease. Further studies are required to determine kinetics and prognostic value of serial measurements of these biomarkers in horses.

Preventive effects of oral probiotic on infantile colic: a prospective, randomised, blinded, controlled trial using Lactobacillus reuteri DSM 17938.

Infants were recruited in four centres in North-West Italy. 138 infants were assessed for eligibility, 113 ones underwent randomisation and 105 completed the study. Newborns aged less than 10 days of life, with gestational age between 37 and 42 weeks, birth weight from 2,500 to 4,300 g and normal physical examination were recruitable. Premature infants and infants affected by outcomes of perinatal hypoxia or necrotising enterocolitis have been excluded. Patients were randomly assigned to receive five drops containing Lactobacillus reuteri DSM 17938 (108 cfu) with 400 UI of vitamin D3 or only 400 UI of vitamin D3 daily. The primary endpoints concern the administration of pain relieving agents (cimetropium bromide at least three times per week or simethicone at least five times per week) from baseline to 12 weeks. Additional analyses were done on the percentage of infants that switched from an exclusive breastfeeding to a partial or exclusive formula feeding from baseline to 12 weeks. Data concerning the number of calls to the paediatricians and the number of visits at paediatricians' ambulatories due to infantile colic have been collected by paediatrician and analysed. Comparing the two groups, the relative risk was 0.04 (95% confidence interval (CI)=0.01-0.31) for cimetropium bromide, 0.24 (95% CI=0.14-0.41) for simethicone and 0.37 (95% CI=0.17-0.80) for the administration of infant formula, showing a protective action of L. reuteri. The treatment group showed a lower number of paediatric consultations related to episodes of infant colic than the control group (P<0.0001). L. reuteri DSM 17938 supplementation at the tested dosage could reduce parental discomfort due to infantile colic. The consumption of this probiotic is associated with a reduction of paediatric consultations for infantile colic, as well as use of pain relieving agents and of infant formula.

Cardiac troponin I concentrations in horses with colic.

OBJECTIVE: To determine prevalence of myocardial injury in horses with colic on the basis of high concentrations of cardiac troponin I (cTnI), frequency of cardiac arrhythmias within the first 24 to 48 hours after hospital admission or surgery because of colic, and associations between high cTnI concentrations and cardiac arrhythmias, clinical course, and outcome (survival to discharge from hospital vs nonsurvival [death or euthanasia]). DESIGN: Prospective observational study. ANIMALS: 111 horses with colic. PROCEDURES: Blood was drawn at admission and 12 and 24 hours after admission if horses were treated medically or 12 and 24 hours after surgery if treated surgically. A 24-hour ambulatory ECG was recorded beginning the morning after admission in medically treated cases or after surgery and evaluated for arrhythmias. Clinical and clinicopathologic data and outcome were obtained. Associations between cTnI concentrations and other variables were determined. RESULTS: An abnormal cTnI concentration (≥ 0.10 ng/mL) at admission was significantly associated with the occurrence of ventricular arrhythmias, outcome, and surgical treatment. CONCLUSIONS AND CLINICAL RELEVANCE: The data suggested that horses with colic and high cTnI concentrations at admission were more likely to have ventricular arrhythmias and have a less favorable prognosis for recovery. High cTnI concentrations in horses with colic were suggestive of myocardial damage.

Expression of PGP 9.5 by enteric neurons in horses and donkeys with and without intestinal disease.

Intestinal motility disorders are an important problem in horses and donkeys and this study was carried out in order to evaluate the enteric neurons in animals with and without intestinal disease. Surplus intestinal tissue samples were collected from 28 horses undergoing exploratory laparotomy for colic. In addition, surplus intestinal samples from 17 control horses were collected immediately following humane destruction for clinical conditions not relating to the intestinal tract. Similar samples were also collected during routine post-mortem examinations from 12 aged donkeys; six animals were humanely destroyed for conditions related to the intestinal tract, while the remaining six were humanely destroyed for other reasons including dental and orthopaedic diseases. Tissue samples were fixed in formalin and immunohistochemical labelling was performed targeting the enteric neurons using a polyclonal antibody specific for the neuronal marker PGP 9.5. The distribution and density of neuronal networks were assessed qualitatively and semiquantitatively. There was strong PGP 9.5 expression in both the horse and donkey samples and labelling was detected throughout the tissue sections. In both species, PGP 9.5-immunoreactive nerve fibres were detected in all layers of the intestinal tract, both in large and small intestinal samples. Networks of enteric neurons were present in the donkey with a similar distribution to that seen in the horse. There was no demonstrable difference in enteric neuronal density and distribution in the groups of animals with intestinal disease compared with those without, apart from two (out of 28) horses with intestinal disease that showed a marked reduction in PGP 9.5 immunoreactivity. Apart from these two animals, this total cohort analysis differs from some previously observed findings in horses with intestinal disease and may therefore reflect the different pathophysiological processes occurring in varying intestinal conditions resulting in colic both in the donkey and the horse.

Associations between infants' crying, sleep and cortisol secretion and mother's sleep and well-being.

BACKGROUND: Infants' continuous crying is a challenge both for the child and the principal caregiver. However, the links between infants' sleep, crying and cortisol secretion and mothers' well-being and sleep have been scarcely investigated. The aim of the present study was therefore to examine the link between cortisol secretion, crying and sleep of infants characterized by infantile colic (IC) and mothers' psychological well-being and own sleep. METHODS: Mothers of 24 infants characterized by IC (mean age = 8 weeks, SD = 1.5 weeks) completed a series of questionnaires regarding the infant's crying and sleeping patterns. Infants' sleep was objectively assessed with actigraphs. Cortisol secretion was measured by means of saliva samples in the mornings after waking. After 4 weeks, infants were assessed once again. Mothers completed questionnaires assessing their psychological well-being (depressive symptoms, family strain) and sleep. RESULTS: Mothers' psychological well-being and sleep was greatly predicted by infants' morning saliva cortisol levels, sleep disruptions and crying intensity, whereas infants' crying duration and volume had low predictive value. CONCLUSIONS: Mothers with infants characterized by IC are at increased risk for reporting impaired sleep, developing depressive symptoms and reporting higher family strain. Most importantly, this risk seems to be greater if their infants' sleep is fragmented.

Evaluation of neutrophil apoptosis in horses with acute abdominal disease.

OBJECTIVE: To quantify peripheral blood neutrophil apoptosis in equine patients with acute abdominal disease (ie, colic) caused by strangulating or nonstrangulating intestinal lesions and compare these values with values for horses undergoing elective arthroscopic surgery. ANIMALS: 20 client-owned adult horses. PROCEDURES: Peripheral blood was collected from horses immediately prior to and 24 hours after surgery for treatment of colic (n = 10) or elective arthroscopic surgery (10), and neutrophils were counted. Following isolation by means of a bilayer colloidal silica particle gradient and culture for 24 hours, the proportion of neutrophils in apoptosis was detected by flow cytometric evaluation of cells stained with annexin V and 7-aminoactinomycin D. Values were compared between the colic and arthroscopy groups; among horses with colic, values were further compared between horses with and without strangulating intestinal lesions. RESULTS: Percentage recovery of neutrophils was significantly smaller in preoperative samples (median, 32.5%) and in all samples combined (35.5%) for the colic group, compared with the arthroscopy group (median, 66.5% and 58.0%, respectively). No significant differences in the percentages of apoptotic neutrophils were detected between these groups. Among horses with colic, those with strangulating intestinal lesions had a significantly lower proportion of circulating apoptotic neutrophils in postoperative samples (median, 18.0%) than did those with nonstrangulating lesions (66.3%). CONCLUSIONS AND CLINICAL RELEVANCE: The smaller proportion of apoptotic neutrophils in horses with intestinal strangulation suggested that the inflammatory response could be greater or prolonged, compared with that of horses with nonstrangulating intestinal lesions. Further investigations are needed to better understand the relationship between neutrophil apoptosis and inflammation during intestinal injury.

Heap of stones: an unusual cause for biliary colic and elevated liver function tests.

A 40-year old woman presented with symptomatic intrahepatic gallstones in one liver segment only four years after cholecystectomy for cholelithiasis. Multiple small, yellow and round calculi were completely removed from the intrahepatic bile ducts via ERCP. The young age of the patient, recurrence of gallstones after cholecystectomy and intrahepatic gallstones suggested a subtype of the low-phospholipid associated cholelithiasis syndrome, a monogenic form of cholesterol cholelithiasis due to variations of the ABCB4 gene that encodes the canalicular phospholipid transporter MDR3.

Use of serial measurements of peritoneal fluid lactate concentration to identify strangulating intestinal lesions in referred horses with signs of colic.

OBJECTIVE: To determine the value of serial measurements of peritoneal fluid lactate concentration (PFL) for detecting strangulating intestinal lesions (SLs) in referred horses with signs of colic. DESIGN: Retrospective cohort study. ANIMALS: 94 horses with signs of colic. PROCEDURES: Medical records of horses evaluated between September 2006 and February 2010 because of signs of colic were reviewed. All included horses had ≥ 2 peritoneal fluid samples collected, including one at admission and another within 1 to 6 hours after admission. Of the 94 horses, 26 were assigned to the SL group on the basis of findings at surgery or necropsy and 68 were assigned to the nonstrangulating intestinal lesion group because their signs of colic resolved with medical management. Peritoneal fluid lactate concentration was measured by use of a handheld lactate monitor. Data were analyzed by use of univariable and multivariable logistic regression analysis. RESULTS: PFL at admission > 4 mmol/L, an increase in PFL over time, and especially an increase in PFL over time in horses with a PFL < 4 mmol/L at admission (OR, 62; sensitivity, 95%; specificity, 77%) were significant predictors of horses with an SL. CONCLUSIONS AND CLINICAL RELEVANCE: Serially determined PFL was a strong predictor for differentiating horses with SLs from horses with nonstrangulating intestinal lesions. Given the high OR, sensitivity, and specificity of these tests, serially determined PFL may have potential as a screening test for identifying horses with SLs. Further evaluation of the clinical value of PFL for predicting SLs in a prospective, multicenter study is warranted.

Peritoneal and plasma D-lactate concentrations in horses with colic.

OBJECTIVE: To evaluate the association between peritoneal fluid and plasma d-lactate concentration with variables used in the diagnosis and prognosis of horses with colic. ANIMALS: Clinically healthy horses (n=6) and 90 horses with colic. STUDY DESIGN: Prospective cross-sectional study. METHODS: D-lactate concentration was determined in peritoneal fluid and plasma of all horses. Information on other blood and peritoneal fluid variables, signalment, results from the physical examination, outcome, need for surgery, lesion location, and type was retrieved from medical records. RESULTS: Peritoneal D-lactate concentration was strongly correlated with plasma D-lactate concentration (r=0.71; P<.001). Peritoneal and plasma D-lactate concentrations were positively correlated with peritoneal (r=0.8; P<.001) and plasma L-lactate (r=0.33; P=.001) concentrations, respectively. Peritoneal D-lactate concentration was negatively correlated with survival to discharge (U=430.5; P<.001). Median peritoneal D-lactate concentration of horses with septic peritonitis (455.2 µmol/L) and horses with gastrointestinal rupture (599.5 µmol/L) were higher compared with horses with nonstrangulating obstructions (77.7 µmol/L). A cut-off concentration of peritoneal D-lactate of 116.6 µmol/L had a sensitivity of 0.813 and a specificity of 0.651 to differentiate between nonstrangulating and strangulating obstructions. CONCLUSIONS: Peritoneal D-lactate concentration may be more useful for identifying horses with strangulating obstructions (high sensitivity, low probability of a false negative) than to ruling out strangulating obstruction (moderate specificity, high probability of a false positive).

Design, synthesis, and pharmacological evaluation of novel hybrid compounds to treat sickle cell disease symptoms.

A novel series of thalidomide derivatives (4a-f) designed by molecular hybridization were synthesized and evaluated in vitro and in vivo for their potential use in the oral treatment of sickle cell disease symptoms. Compounds 4a-f demonstrated analgesic, anti-inflammatory, and NO-donor properties. Compounds 4c and 4d were considered promising candidate drugs and were further evaluated in transgenic sickle cell mice to determine their capacity to reduce the levels of the proinflammatory cytokine tumor necrosis factor α (TNFα). Unlike hydroxyurea, the compounds reduced the concentrations of TNFα to levels similar to those induced with the control dexamethasone (300 µmol/kg). These compounds are novel lead drug candidates with multiple beneficial actions in the treatment of sickle cell disease symptoms and offer an alternative to hydroxyurea treatment.

'Oh, baby, please don't cry!': in infants suffering from infantile colic hypothalamic-pituitary-adrenocortical axis activity is related to poor sleep and increased crying intensity.

BACKGROUND/AIM: Infantile colic (IC) is considered to represent the upper end of the spectrum of early developmental crying behavior. Little is known about hypothalamic-pituitary-adrenocortical axis activity and sleep in relation to infants' crying. The aim of the present study was to assess cortisol secretion in infants in relation to their sleep and crying patterns. METHOD: Sixteen infants (mean age: 8 weeks; SD = 1.5 weeks) were enrolled. Their mothers completed a series of questionnaires regarding the infants' crying and sleeping patterns. The infants' sleep was objectively assessed with actigraphs. After 4 weeks, the infants were assessed once again. Cortisol secretion was measured by means of saliva samples in the mornings after awakening. RESULTS: Morning saliva cortisol levels were related to more frequent awakening and to increased crying intensity, but not to sleep or crying duration. Over 4 weeks, both crying behavior and sleep duration decreased, but there was no association between them. Cortisol secretion did not significantly change. CONCLUSIONS: In infants suffering from IC, fragmented sleep patterns and increased saliva cortisol levels were related. Cortisol secretion seems to be related to crying intensity, but not to crying duration. Crying intensity may reflect greater physiological or psychological stress rather than mere duration of crying.