Improvement of point of care testing (POCT) device for accurate whole blood glucose measurement in early neonates.

BACKGROUND: It is important that blood glucose concentrations be accurately and conveniently measured in infants. However, especially in the early neonatal period, point-of-care testing devices used for adults may not accurately measure blood glucose concentrations in neonates. METHODS: In Study 1, the accuracy of neonatal whole-blood glucose measurements was evaluated for the existing glucose analyser Glutest Mint® (hereinafter MINT1; Sanwa Kagaku Kenkyusho, Nagoya, Japan) by comparing the data with reference blood glucose concentrations. In Study 2, we used MINT2, which was modified based on the findings from Study 1, to measure whole-blood glucose concentrations in newborns, and the accuracy of the measurements was compared with that of MINT1. RESULTS: Blood glucose concentrations were measured in 100 infants each in Study 1 and 2. In Study 1, the whole-blood glucose concentrations measured using MINT1 were found to be significantly lower than the reference blood glucose concentrations in early neonates. The results of Study 1 suggested that characteristics of erythrocyte membranes in early neonates affected the measurements. Therefore, we conducted Study 2 using MINT2, which was modified to be less susceptible. MINT2 was found to accurately measure whole-blood glucose concentrations in the early neonatal period. CONCLUSION: The study showed that the point-of-care testing device could be improved to allow for accurate whole-blood glucose measurements in the early neonatal period.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.

Developmental changes in neonatal hemodynamics during tactile stimulation using whole-head functional near-infrared spectroscopy.

Neural-activity-associated hemodynamic changes have been used to noninvasively measure brain function in the early developmental stages. However, the temporal changes in their hemodynamics are not always consistent with adults. Studies have not evaluated developmental changes for a long period using the same stimuli; therefore, this study examined the normalized relative changes in oxygenated hemoglobin (Δ[oxy-Hb]) in full-term infants and compared them with neonates up to 10 months of age during the administration of tactile vibration stimuli to their limbs using whole-head functional near-infrared spectroscopy. The time to peak of normalized Δ[oxy-Hb] was not affected by age. The amplitude of normalized Δ[oxy-Hb] showed an effect of age in broader areas, including sensorimotor-related but excluding supplementary motor area; the amplitude of normalized Δ[oxy-Hb] decreased the most in the 1-2-month-old group and later increased with development. We hypothesized that these results may reflect developmental changes in neural activity, vasculature, and blood oxygenation.

Developmental changes in visual-cognitive and attentional functions in infancy.

BACKGROUND: Identifying developmental changes in visual-cognitive and attentional functions during infancy may lead to early diagnosis of neurodevelopmental disorders such as ASD and ADHD. AIMS: To clarify the developmental changes in visual-cognitive and attentional functions during infancy (3-36 months of age). STUDY DESIGN: Cross-sectional study. SUBJECTS: We included 23, 24, 31, and 26 participants aged 3, 9, 18, and 36 months, respectively (full-term births). Fifteen children who cried intensely or whose data could not be accurately recorded were excluded. OUTCOME MEASURES: Three activities were given to each child while they were seated in front of a gaze-tracking device to evaluate re-gaze, motion transparency, and color-motion integration. We analyzed whether the child's attention shifted to the new stimulus in their peripheral vision in the re-gaze task. In the motion transparency and color-motion integration tasks, two images were presented simultaneously on the screen. In the motion transparency task, participants preferred random dots moving in opposite directions; in the color-motion task, they preferred subjective contours from apparent motion stimuli consisting of random red and green dots with different luminance. RESULTS: In the re-gaze task, fewer 3-month-olds gazed at the new target than other age groups participants. All ages showed preference for target stimuli in the motion transparency task, but 3-month-olds showed significantly lower preference in the color-motion integration task. CONCLUSION: These tasks may be useful for measuring visual-cognitive and attentional functions in infants.

Conflicting findings on the effectiveness of hydrogen therapy for ameliorating vascular leakage in a 5-day post hypoxic-ischemic survival piglet model.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in newborns in both high- and low-income countries. The important determinants of its pathophysiology are neural cells and vascular components. In neonatal HIE, increased vascular permeability due to damage to the blood-brain barrier is associated with seizures and poor outcomes in both translational and clinical studies. In our previous studies, hydrogen gas (H2) improved the neurological outcome of HIE and ameliorated the cell death. In this study, we used albumin immunohistochemistry to assess if H2 inhalation effectively reduced the cerebral vascular leakage. Of 33 piglets subjected to a hypoxic-ischemic insult, 26 piglets were ultimately analyzed. After the insult, the piglets were grouped into normothermia (NT), H2 ventilation (H2), therapeutic hypothermia (TH), and H2 combined with TH (H2-TH) groups. The ratio of albumin stained to unstained areas was analyzed and found to be lower in the H2 group than in the other groups, although the difference was not statistically significant. In this study, H2 therapy did not significantly improve albumin leakage despite the histological images suggesting signs of improvement. Further investigations are warranted to study the efficacy of H2 gas for vascular leakage in neonatal HIE.

Serum caffeine concentrations in preterm infants: a retrospective study.

Therapeutic drug monitoring is generally unnecessary in caffeine treatment for apnea of prematurity, as serum caffeine concentrations in preterm infants are normally markedly lower than those at which caffeine intoxication occurs. However, several studies have reported preterm infants having developed toxicity. This retrospective observational study, conducted at a tertiary center in Kagawa, Japan, aimed to evaluate the correlation between the maintenance dose and serum caffeine concentrations and determine the maintenance dose leading to suggested toxic caffeine levels. We included 24 preterm infants (gestational age, 27 ± 2.9 weeks; body weight, 991 ± 297 g) who were treated with caffeine citrate for apnea of prematurity between 2018 and 2021, and 272 samples were analyzed. Our primary outcome measure was the maintenance dose leading to suggested toxic caffeine levels. We found a positive correlation between caffeine dose and serum caffeine concentrations (p < 0.05, r = 0.72). At doses of ≥ 8 mg/kg/day, 15% (16/109) of patients had serum caffeine concentrations above the suggested toxic levels. Patients who receive doses ≥ 8 mg/kg/day risk reaching the suggested toxic serum caffeine levels. It remains unclear whether suggested toxic caffeine concentrations are detrimental to neurological prognosis. Further investigation is required to understand the clinical effects/outcomes of high serum levels of caffeine and to obtain long-term neurodevelopmental follow-up data.

Neonatal asphyxia as an inflammatory disease: Reactive oxygen species and cytokines.

Neonatologists resuscitate asphyxiated neonates by every available means, including positive ventilation, oxygen therapy, and drugs. Asphyxiated neonates sometimes present symptoms that mimic those of inflammation, such as fever and edema. The main pathophysiology of the asphyxia is inflammation caused by hypoxic-ischemic reperfusion. At birth or in the perinatal period, neonates may suffer several, hypoxic insults, which can activate inflammatory cells and inflammatory mediator production leading to the release of larger quantities of reactive oxygen species (ROS). This in turn triggers the production of oxygen stress-induced high mobility group box-1 (HMGB-1), an endogenous damage-associated molecular patterns (DAMPs) protein bound to toll-like receptor (TLR) -4, which activates nuclear factor-kappa B (NF-κB), resulting in the production of excess inflammatory mediators. ROS and inflammatory mediators are produced not only in activated inflammatory cells but also in non-immune cells, such as endothelial cells. Hypothermia inhibits pro-inflammatory mediators. A combination therapy of hypothermia and medications, such as erythropoietin and melatonin, is attracting attention now. These medications have both anti-oxidant and anti-inflammatory effects. As the inflammatory response and oxidative stress play a critical role in the pathophysiology of neonatal asphyxia, these drugs may contribute to improving patient outcomes.

Quantitative effects of bilirubin structural photoisomers on the measurement of direct bilirubin via the vanadate oxidation method.

BACKGROUND: Exposing blood serum samples to ambient white light-emitting diode (WLED) light may accelerate bilirubin photoisomer production. We previously demonstrated the quantitative effect of bilirubin configurational isomers (BCI) on direct bilirubin (DB) value using the vanadate oxidation method. However, the effects of bilirubin structural photoisomers (BSI) remain unclear. METHODS: In Study 1, the relationship between WLED irradiation time and BSI production was examined. Serum samples from five neonates were irradiated with WLED light for 0, 10, 30, 60 and 180 min. Bilirubin isomer concentration and BSI production rates were calculated. In Study 2, we performed quantitative investigation of BSI effect on DB values: Differences in DB, BCI and BSI values before and after irradiation were calculated as ⊿DB, ⊿BCI and ⊿BSI, respectively. Assuming the coefficient of BCI affecting DB values was 'a', relational expression was ⊿DB = a*⊿BSI + 0.19*⊿BCI. Serum samples from 15 neonates were irradiated with green LED light for 10 and 30 s. The respective bilirubin isomer levels were measured, and the coefficient was derived. RESULTS: In Study 1, the median BSI production rate was 0.022 mg/dL per min in specimens with an unconjugated bilirubin concentration of 10.88 mg/dL. In Study 2, assuming that ⊿DB-0.19*⊿BCI was Y and ⊿BSI was X, the relational expression was Y = 0.34X-0.03 (R2 = 0.87; p < .01) and a = 0.34. CONCLUSIONS: Under ambient WLED light, serum sample generated 1.3 mg/dL BSIs in 1 h. Approximately 34% (0.44 mg/dL) of BSI concentrations was measured as DB when using the vanadate oxidation method according to the above equation.

Chlamydia trachomatis relies on the scavenger role of aryl hydrocarbon receptor with detyrosinated tubulin for its intracellular growth, but this is impaired by excess indole.

Although IFN-γ depletes tryptophan (Trp) as a defense against intracellular Chlamydia trachomatis (Ct) infected to hypoxic vagina, the presence of indole, a precursor of Trp, enables Ct to infect IFN-γ-exposed culture cells. Meanwhile, Trp-derived indole derivatives interact the aryl hydrocarbon receptor (AhR), which is a ligand-dependent transcription factor involved in the cellular homeostasis with tubulin dynamics. Here, the amounts of IFN-γ and indole in cervical swabs with known Ct infection status were measured, and Ct growth in the presence of indole was determined from the perspective of the AhR axis under hypoxia. A positive correlation between the amounts of IFN-γ and indole was found, and both of these amounts were lower in Ct-positive swabs than in Ct-negative ones. Indole as well as other AhR ligands inhibited Ct growth, especially under normoxia. Ct prompted the expression of detyrosinated tubulin (dTTub), but indole inhibited it. Indole did not stimulate the translocation of AhR to nucleus, and it blocked AhR activation in AhR-reporter cells. Ct growth was reduced more effectively under normoxia in AhR-knockdown cells, an effect that was enhanced by indole, which in turn diminished dTTub. Thus, Ct growth relies on the scavenger role of cytosolic AhR responsible for promoting dTTub expression.

Impact of hydrogen gas inhalation during therapeutic hypothermia on cerebral hemodynamics and oxygenation in the asphyxiated piglet.

We previously reported the neuroprotective potential of combined hydrogen (H2) gas ventilation therapy and therapeutic hypothermia (TH) by assessing the short-term neurological outcomes and histological findings of 5-day neonatal hypoxic-ischemic (HI) encephalopathy piglets. However, the effects of H2 gas on cerebral circulation and oxygen metabolism and on prognosis were unknown. Here, we used near-infrared time-resolved spectroscopy to compare combined H2 gas ventilation and TH with TH alone. Piglets were divided into three groups: HI insult with normothermia (NT, n = 10), HI insult with hypothermia (TH, 33.5 ± 0.5 °C, n = 8), and HI insult with hypothermia plus H2 ventilation (TH + H2, 2.1-2.7%, n = 8). H2 ventilation and TH were administered and the cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation (ScO2) were recorded for 24 h after the insult. CBV was significantly higher at 24 h after the insult in the TH + H2 group than in the other groups. ScO2 was significantly lower throughout the 24 h after the insult in the TH + H2 group than in the NT group. In conclusion, combined H2 gas ventilation and TH increased CBV and decreased ScO2, which may reflect elevated cerebral blood flow to meet greater oxygen demand for the surviving neurons, compared with TH alone.

An enriched environment ameliorates the reduction of parvalbumin-positive interneurons in the medial prefrontal cortex caused by maternal separation early in life.

Early child maltreatment, such as child abuse and neglect, is well known to affect the development of social skills. However, the mechanisms by which such an adverse environment interrupts the development of social skills remain unelucidated. Identifying the period and brain regions that are susceptible to adverse environments can lead to appropriate developmental care later in life. We recently reported an excitatory/inhibitory imbalance and low activity during social behavior in the medial prefrontal cortex (mPFC) of the maternal separation (MS) animal model of early life neglect after maturation. Based on these results, in the present study, we investigated how MS disturbs factors related to excitatory and inhibitory neurons in the mPFC until the critical period of mPFC development. Additionally, we evaluated whether the effects of MS could be recovered in an enriched environment after MS exposure. Rat pups were separated from their dams on postnatal days (PDs) 2-20 (twice daily, 3 h each) and compared with the mother-reared control (MRC) group. Gene expression analysis revealed that various factors related to excitatory and inhibitory neurons were transiently disturbed in the mPFC during MS. A similar tendency was found in the sensory cortex; however, decreased parvalbumin (PV) expression persisted until PD 35 only in the mPFC. Moreover, the number of PV+ interneurons decreased in the ventromedial prefrontal cortex (vmPFC) on PD 35 in the MS group. Additionally, perineural net formation surrounding PV+ interneurons, which is an indicator of maturity and critical period closure, was unchanged, indicating that the decreased PV+ interneurons were not simply attributable to developmental delay. This reduction of PV+ interneurons improved to the level observed in the MRC group by the enriched environment from PD 21 after the MS period. These results suggest that an early adverse environment disturbs the development of the mPFC but that these abnormalities allow room for recovery depending on the subsequent environment. Considering that PV+ interneurons in the mPFC play an important role in social skills such as empathy, an early rearing environment is likely a very important factor in the subsequent acquisition of social skills.

High intestinal vascular permeability in a murine model for Hirschsprung's disease: implications for postoperative Hirschsprung-associated enterocolitis.

PURPOSE: Intestinal vascular permeability (VP) in a murine model for Hirschsprung's disease (HD) and postoperative Hirschsprung-associated enterocolitis (HAEC) were investigated. METHODS: Intestinal VP was determined using a Miles assay using 1% Evans blue injected into a superficial temporal vein of newborn endothelin receptor-B KO HD model (KO) and syngeneic wild-type (WT) mice (n = 5, respectively). Extravasated Evans blue in normoganglionic ileum (Ng-I), normoganglionic proximal colon (Ng-PC) and aganglionic distal colon (Ag-DC) was quantified by absorbance at 620 nm. Quantitative polymerase chain reaction (qPCR) for Vascular Endothelial Growth Factor A (VEGF-A), VEGF-B, CDH5, SELE and CD31, and immunofluorescence for CD31 were performed. RESULTS: VP was significantly higher in Ng-I, Ng-PC, and Ag-DC from KO than WT (p < 0.01, p < 0.05, and p < 0.05, respectively). qPCR demonstrated upregulated VEGF-A in Ng-I and Ag-DC, VEGF-B in Ng-I, and SELE in Ng-I and Ng-PC (p < 0.05, p < 0.05, p < 0.05, p < 0.01 and p < 0.05, respectively), and downregulated CDH5 in Ng-I and Ng-PC from KO (p < 0.05, respectively). Expression of CD31 mRNA in Ng-I and Ag-DC from KO was significantly higher on qPCR (p < 0.05) but differences on immunofluorescence were not significant. CONCLUSIONS: VP may be etiologic for postoperative HAEC throughout the intestinal tract even after excision of aganglionic bowel.

[A Case of Perforation of Unresectable Esophageal Cancer during Nivolumab Therapy].

A 46-year-old man visited our hospital complaining of dysphagia. He was diagnosed with unresectable esophageal cancer with multiple lung metastases(cStage Ⅳb)and gastric cancer(L, Gre, T3N+M0, cStage Ⅲ). The esophageal lesion and the lung metastatic lesions showed shrinkage initially with 5-FU, CDDP(FP)therapy but then re-grew; therefore, the therapy was changed to nivolumab therapy. After three courses of nivolumab therapy, the patient visited our hospital with a high fever. He was admitted as an emergency patient with a diagnosis of esophageal perforation and mediastinal abscess. CT- guided drainage was performed, and a self-expanding metal stent(SEMS)was placed. He was discharged on the 31st day of hospitalization and nivolumab therapy was resumed. We report the first case of esophageal perforation during immunotherapy with nivolumab therapy for esophageal cancer.

Age­related differences for expression of the nerve­specific proteins after peripheral nerve injury.

The effects of aging on axon regeneration currently remain unclear. In addition, the up-regulated expression of neurotrophic factors that occurs within one week of peripheral nerve injury has been shown to play an important role in the axon regeneration. To investigate the effects of aging on axon regeneration, the expression of nerve-specific proteins immediately after peripheral nerve injury were compared between young and aged mice. A mouse peripheral nerve injury model was prepared using the sciatic nerve compression method. In each group, Luxol fast blue staining and immunofluorescence staining were performed to assess the degree of Wallerian degeneration in the sciatic nerve, and to evaluate the expression of repressor element 1-silencing transcription factor (REST)/neuron-restrictive silencer factor (NRSF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), nerve growth factor (NGF), and semaphorin 3A (Sema3A) in the dorsal root ganglion, respectively. Wallerian degeneration was observed in both young and aged mice after peripheral nerve injury. Significant increases were observed in the expression of REST/NRSF (P<0.0001), NT3 (P=0.0279), and Sema3A (P=0.0175) following peripheral nerve injury in young mice, while that of BDNF (P=0.5583) and NGF (P=0.9769) remained unchanged. On the other hand, no significant differences were noted in the expression of these nerve-specific proteins in aged mice. Based on the results of the present study, compensatory changes induced by peripheral nerve injury were initiated by the up-regulated expression of REST/NRSF in young mice, but not in aged mice.

Association between bile area in the duodenal bulb and abdominal symptoms: Quantitative analysis using blue laser imaging.

Bile acids are strongly associated with the pathogenesis of functional gastrointestinal diseases. In recent years, blue laser imaging (BLI) endoscopy has emerged as a novel image-enhanced endoscopic method, which illustrates bile as a reddish hue. The present study investigated the factors that affect the area of bile in duodenal bulbs using BLI. For this purpose, patients (356 cases) who underwent upper endoscopy with BLI between April, 2017 and December, 2019, and completed patient background and symptom questionnaires [Constipation Scoring System (CSS), Bristol Stool Form Scale (BSFS) and Frequency Scale for Symptoms of gastroesophageal reflux disease (FSSG)], were retrospectively investigated. Each BLI bile score was calculated as a percentage of bile area in a field of view in the duodenal bulb using a KS400 image analysis system, and the association with abdominal symptoms was examined using multiple regression analysis. The patient characteristics included the following: Age (in years), 69.9±11.3; male/female ratio, 146/210; body mass index, 23.0±3.8; reflux esophagitis (M/A/B/C), 143/19/3/3; atrophic gastritis (C-0/C1-3/O1-3), 132/100/124; proton pump inhibitor potassium competitive acid blocker/aspirin/ursodeoxycholic acid/gall bladder stones/cholecystectomy, 105/27/18/43/18; BLI bile score, 7.10 (±14.34); CSS score, 3.55 (±3.80); BSFS score, 3.91 (±1.02); and FSSG score, 4.80 (±5.76). Correlation coefficients (P<0.05) for the BLI bile score were found for cholecystectomy (Rho=0.137) and aspirin use (Rho=0.118). In multiple regression analysis, independent predictors of the BLI bile score were cholecystectomy [standardized partial regression coefficient (ß)=0.169, P=0.001] and the BSFS score (ß=0.107, P=0.042). On the whole, the present study demonstrates that the duodenal bile area in BLI upper endoscopy is associated with cholecystectomy and fecal characteristics.

Transcutaneous bilirubin-based screening reduces the need for blood exchange transfusion in Myanmar newborns: A single-center, retrospective study.

Background: Neonatal hyperbilirubinemia is a significant health problem in Myanmar. We introduced transcutaneous bilirubin (TcB) measurements in 2017 and developed an hour-specific TcB nomogram for early detection and treatment of hyperbilirubinemia in Myanmar neonates. This study aimed to evaluate whether our screening method for hyperbilirubinemia decreased the requirement of blood exchange therapy (ET). Methods: This retrospective cohort study was conducted at the Central Women's Hospital, Yangon. Two groups were included as follows: group 1 (control group; comprising infants born in 2016 and screened on the basis of Kramer's rule), and group 2 (intervention group; comprising infants born in 2019 and screened by TcB measurement using a nomogram). The number of ETs was analyzed based on causes of hyperbilirubinemia and number of days after birth. Results: Groups 1 and 2 comprised 12,968 and 10,090 infants, respectively. Forty-six and two infants in Groups 1 and 2, respectively, required an ET. The odds ratio for ET was 18.0 (Group 1 to Group 2; 95% confidence interval [CI]: 4.8-67.1; p = 0.000). Serum bilirubin values at the time ET was administered were significantly higher in Group 1 than those in Group 2 (median: 23.0 and 16.8, respectively). Conclusion: The management of hyperbilirubinemia using our screening method (TcB Nomogram) can effectively reduce the need for ET in neonates in Myanmar.

Cerebral hemodynamic response during the resuscitation period after hypoxic-ischemic insult predicts brain injury on day 5 after insult in newborn piglets.

Perinatal hypoxic-ischemic brain injury of neonates remains a significant problem worldwide. During the resuscitation period, changes in cerebral hemoglobin oxygen saturation (ScO2) have been identified by near-infrared spectroscopy (NIRS). However, in asphyxiated neonates, the relationship between these changes and brain injury is not known. Three-wavelength near-infrared time-resolved spectroscopy, an advanced technology for NIRS, allows for the estimation of ScO2 and cerebral blood volume (CBV). Here, we studied changes in ScO2 and CBV during the resuscitation period after hypoxic-ischemic insult and the relationship between these changes after insult and histopathological brain injuries on day 5 after insult using an asphyxiated piglet model. Of 36 newborn piglets subjected to hypoxic-ischemic insult, 29 were analyzed. ScO2 and CBV were measured 0, 5, 10, 15, and 30 min after the insult. Brain tissue was histologically evaluated on day 5. ScO2 and CBV increased immediately after the insult, reached a peak, and then maintained a consistent value. The increase in CBV 5 to 30 min after the insult was significantly correlated with histopathological injury scores. However, there was no correlation with ScO2. In conclusion, an increase in CBV within 30 min after hypoxic-ischemic insult reflects the histopathological brain injury on day 5 after insult in a piglet model.

Chlamydia trachomatis L2/434/Bu Favors Hypoxia for its Growth in Human Lymphoid Jurkat Cells While Maintaining Production of Proinflammatory Cytokines.

The role of lymphocytes as a cornerstone of the inflammatory response in the invasive pathogenesis of Chlamydia trachomatis (Ct) LGV (L1-3) infection is unclear. Therefore, we assessed whether the adaptation of CtL2 to immortal lymphoid Jurkat cells under hypoxic conditions occurred through proinflammatory cytokine profile modification. The quantities of inclusion-forming units with chlamydial 16S rDNA confirmed that CtL2 grew well under hypoxic rather than normoxic conditions in the cells. Confocal microscopic imaging and transmission electron microscopy revealed the presence of bacterial progeny in the inclusions and showed that the inclusions were larger under hypoxic rather than normoxic conditions; this was supported by the results of 3D image construction. Furthermore, PCR-based analysis of proinflammatory cytokines revealed that the gene expression levels under hypoxic conditions were significantly higher than those under normoxic conditions. In particular, the expression of two genes (CXCL8 and CXCR3) was significantly diminished under normoxic conditions. Taken together, the results indicated that hypoxia promoted CtL2 growth in Jurkat cells while maintaining the levels of proinflammatory cytokines. Thus, Ct LGV infection in lymphocytes under hypoxic conditions might be crucial to a complete understanding of the invasive pathogenesis.

A case of acute appendicitis incarcerated in obturator hernia.

An 85 year-old woman was transferred with a chief complaint of right thigh pain persisting for 5 days. Abdominal contrast-enhanced computed tomography clearly depicted a swollen appendix incarcerated in the right obturator cavity. She underwent an emergent laparoscopic appendectomy and the simultaneous repair of the obturator hernia. At laparoscopy, appendix was found to be incarcerated in the right obturator canal. The incarcerated appendix was successfully flushed out from the sac by spurting saline into the obturator hernia sac through the catheter inserted into the hernia sac. After a laparoscopic appendectomy, the hernia orifice was repaired using the uterine flap. The patient was discharged from the hospital without any sequelae. This report demonstrates a very rare case of obturator hernia incarcerated with appendix. Although patients with obturator hernia incarcerated with small intestine present with the symptoms related to bowel obstruction, patients with incarceration of appendix do not. Moreover, they would show no typical abdominal symptoms associated with acute appendicitis. Therefore, it is important to perform a radiological evaluation promptly to make a definitive diagnosis when a patient with persisting pain of the right thigh or right ileac fossa with a possibility of obturator hernia with incarceration of the appendix is encountered.