Hedonic drinking engages a supra-spinal inhibition of thermal nociception in adult rats

The taste of sucrose is commonly used to provide pain relief in newborn humans and is innately analgesic to neonatal rodents. In adulthood, sucrose remains a strong motivator to feed, even in potentially hazardous circumstances (ie, threat of tissue damage). However, the neurobiological mechanisms of this endogenous reward–pain interaction are unclear. We have developed a simple model of sucrose drinking–induced analgesia in Sprague–Dawley rats (6-10 weeks old) and have undertaken a behavioral and pharmacological characterization using the Hargreaves' test of hind-paw thermal sensitivity. Our results reveal an acute, potent, and robust inhibitory effect of sucrose drinking on thermal nociceptive behaviour that unlike the phenomenon in neonates is independent of endogenous opioid signalling and does not seem to operate through classical descending inhibition of the spinal cord circuitry. Experience of sucrose drinking had a conditioning effect whereby the apparent expectancy of sucrose enabled water alone (in euvolemic animals) to elicit a short-lasting placebo-like analgesia. Sweet taste alone, however, was insufficient to elicit analgesia in adult rats intraorally perfused with sucrose. Instead, the sucrose analgesia phenomenon only appeared after conditioning by oral perfusion in chronically cannulated animals. This sucrose analgesia was completely prevented by systemic dosing of the endocannabinoid CB1 receptor antagonist rimonabant. These results indicate the presence of an endogenous supraspinal analgesic circuit that is recruited by the context of rewarding drinking and is dependent on endocannabinoid signalling. We propose that this hedonic sucrose-drinking model may be useful for further investigation of the supraspinal control of pain by appetite and reward

Factors Associated with Long-Term Oral Hypoglycemic Agent Responsiveness in Korean Patients with Type 2 Diabetes Mellitus

BackgroundThis study was performed to determine the factors associated with long-term oral hypoglycemic agent (OHA) responsiveness in Korean type 2 diabetic patients.MethodsTwo groups of patients were selected among the type 2 diabetic patients who were followed for more than two years at a university hospital diabetes clinic. The OHA responsive group consisted of 197 patients whose HbA1c levels were maintained at ≤7% with OHA for more than two years. The OHA failure group consisted of 180 patients whose HbA1c levels were >8% in spite of optimal combined OHA therapy or patients who required insulin therapy within the two years of the study.ResultsThe OHA failure group had higher baseline values of fasting and postprandial glucose, HbA1c, and lower fasting, postprandial, and delta C-peptide compared to those of the OHA responsive group. The OHA failure group also had a higher proportion of female patients, longer diabetic duration, and more family history of diabetes. There were no significant differences in body mass index (BMI) or insulin resistance index between the two groups. Multiple logistic regression analysis showed that the highest quartile of baseline fasting, postprandial glucose, and HbA1c and the lowest quartile of postprandial and delta C-peptide were associated with an increased odds ratio of OHA failure after adjustment for age, sex, body mass index, and family history of diabetes.ConclusionLower baseline values of postprandial and delta C-peptide and elevated fasting glucose and HbA1c are associated with long-term OHA responsiveness in Korean patients with type 2 diabetes mellitus

Self-reported pain scores as a predictor of preterm birth in symptomatic twin pregnancy: a retrospective study

Background To evaluate the self-reported pain scores as a predictor of preterm birth (PTB) in symptomatic twin pregnancy and to develop a nomogram for the prediction model. Methods We conducted a retrospective study of 148 cases of symptomatic twin pregnancies before 34 weeks of gestation visited at Seoul national university hospital from 2013 to 2018. With other clinical factors, self-reported pain score was evaluated by the numerical rating scale (NRS) pain scores for pain intensity. By multivariate analyses and logistic regression, we developed a prediction model for PTB within 7 days. Using the Cox proportional hazards model, the curves were plotted to show the predictability of the PTB according to NRS pain score, while adjusting the other covariates. Results Twenty-three patients (15.5 %) delivered preterm within 7 days. By a logistic regression analysis, higher NRS pain score (OR 1.558, 95 % CI 1.093–2.221, P < 0.05), shorter cervical length (OR 3.164, 95 % CI 1.262–7.936, P < 0.05) and positive fibronectin results (OR 8.799, 95 % CI 1.101–70.330, P < 0.05) affect PTB within 7 days. Using the variables, the area under the receiver operating characteristic curve (AUROC) of the prediction model was 0.917. In addition, we developed a nomogram for the prediction of PTB within 7 days. Conclusions Self-reported pain scores combined with cervical length and fetal fibronectin are useful in predicting impending PTB in symptomatic twin pregnancy.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI19C0213)

Sacral Nerve Stimulation for Treatment of Chronic Intractable Anorectal Pain -A Case Report-

Despite recent methodological advancement of the practical pain medicine, many cases of the chronic anorectal pain have been intractable. A 54-year-old female patient who had a month history of a constant severe anorectal pain was referred to our clinic for further management. No organic or functional pathology was found. In spite of several modalities of management, such as medications and nerve blocks had been applied, the efficacy of such treatments was not long-lasting. Eventually, she underwent temporary then subsequent permanent sacral nerve stimulation. Her sequential numerical rating scale for pain and pain disability index were markedly improved. We report a successful management of the chronic intractable anorectal pain via permanent sacral nerve stimulation. But further controlled studies may be needed

Mitochondria directly influence fertilisation outcome in the pig

The mitochondrion is explicitly involved in cytoplasmic regulation and is the cell's major generator of ATP. Our aim was to determine whether mitochondria alone could influence fertilisation outcome. In vitro, oocyte competence can be assessed through the presence of glucose-6-phosphate dehydrogenase (G6PD) as indicated by the dye, brilliant cresyl blue (BCB). Using porcine in vitro fertilisation (IVF), we have assessed oocyte maturation, cytoplasmic volume, fertilisation outcome, mitochondrial number as determined by mtDNA copy number, and whether mitochondria are uniformly distributed between blastomeres of each embryo. After staining with BCB, we observed a significant difference in cytoplasmic volume between BCB positive (BCB+) and BCB negative (BCB-) oocytes. There was also a significant difference in mtDNA copy number between fertilised and unfertilised oocytes and unequal mitochondrial segregation between blastomeres during early cleavage stages. Furthermore, we have supplemented BCB- oocytes with mitochondria from maternal relatives and observed a significant difference in fertilisation outcomes following both IVF and intracytoplasmic sperm injection (ICSI) between supplemented, sham-injected and non-treated BCB- oocytes. We have therefore demonstrated a relationship between oocyte maturity, cytoplasmic volume, and fertilisation outcome and mitochondrial content. These data suggest that mitochondrial number is important for fertilisation outcome and embryonic development. Furthermore, a mitochondrial pre-fertilisation threshold may ensure that, as mitochondria are diluted out during post-fertilisation cleavage, there are sufficient copies of mtDNA per blastomere to allow transmission of mtDNA to each cell of the post-implantation embryo after the initiation of mtDNA replication during the early postimplantation stages

Intraoperative Vertebral Artery Angiography to Guide C1-2 Transarticular Screw Fixation in a Patient with Athetoid Cerebral Palsy

We present a case of an athetoid cerebral palsy with quadriparesis caused by kyphotic deformity of the cervical spine, severe spinal stenosis at the cervicomedullary junction, and atlantoaxial instability. The patient improved after the first surgery, which included a C1 total laminectomy and C-arm guided righ side unilateral C1-2 transarticular screw fixation. C1-2 fixation was not performed on the other side because of an aberrant and dominant vertebral artery (VA). Eight months after the first operation, the patient required revision surgery for persistent neck pain and screw malposition. We used intraoperative VA angiography with simultaneous fluoroscopy for precise image guidance during bilateral C1-2 transarticular screw fixation. Intraoperative VA angiography allowed the accurate insertion of screws, and can therefore be used to avoid VA injury during C1-2 transarticular screw fixation in comorbid patients with atlantoaxial deformities

Characterization and Online Detection of Surfactin Isomers Based on HPLC-MSn Analyses and Their Inhibitory Effects on the Overproduction of Nitric Oxide and the Release of TNF-α and IL-6 in LPS-Induced Macrophages

A rapid method for characterization and online detection of surfactin isomers was developed based on HPLC-MSn (n = 1, 2, 3) analyses, and many surfactin isomers were detected and characterized from the bioactive fraction of the mangrove bacterium Bacillus sp. Inhibitory activities of surfactin isomers on the overproduction of nitric oxide and the release of TNF-α and IL-6 in LPS-induced macrophages were systematically investigated. It was revealed that the surfactin isomers showed strong inhibitory properties on the overproduction of nitric oxide and the release of IL-6 on LPS-induced murine macrophage cell RAW264.7 with IC50 values ranging from 1.0 to 7.0 μM. Structure-activity relationship (SAR) studies revealed that the existence of the free carboxyl group in the structure of surfactin isomers was crucial. These findings will be very helpful for the development of this novel kind of natural product as new anti-inflammatory agents

Anti-obesity activity of diglyceride containing conjugated linoleic acid in C57BL/6J ob/ob mice

This study was to investigate the anti-obesity effects of diglyceride (DG)-conjugated linoleic acid (CLA) containing 22% CLA as fatty acids in C57BL/6J ob/ob male mice. There were four experimental groups including vehicle control, DG, CLA, and DG-CLA. The test solutions of 750 mg/kg dose were orally administered to the mice everyday for 5 weeks. CLA treatments significantly decreased mean body weight in the obese mice throughout the experimental period compared to the control (p < 0.01). All test solutions significantly decreased the levels of triglyceride, glucose and free fatty acids in the serum compared with control (p < 0.05). The levels of total cholesterol were also significantly reduced in DG and DG-CLA groups compared with the control group (p < 0.05). CLA significantly decreased weights of renal and epididymal fats compared with the control (p < 0.05). DG and DG-CLA also significantly decreased the epididymal fat weights compared with the control (p < 0.05). A remarkable decrease in the number of lipid droplets and fat globules was observed in the livers of mice treated with DG, CLA, and DG-CLA compared to control. Treatments of DG and CLA actually increased the expression of peroxisome proliferator-activated receptor gamma. These results suggest that DG-CLA containing 22% CLA have a respectable anti-obesity effect by controlling serum lipids and fat metabolism