-
Molecules (Basel, Switzerland) May 2023Co-hydrothermal carbonization (co-HTC) of N-rich and lignocellulosic biomass is a potential way to produce hydrochar with high yield and quality, but the nitrogen will...
The Role of the Mannich Reaction in Nitrogen Migration during the Co-Hydrothermal Carbonization of Bovine Serum Albumin and Lignin with Various Forms of Acid-Alcohol Assistance.
Co-hydrothermal carbonization (co-HTC) of N-rich and lignocellulosic biomass is a potential way to produce hydrochar with high yield and quality, but the nitrogen will also enrich in a solid product. In this study, a novel co-HTC with acid-alcohol assistance is proposed, and the model compounds bovine serum albumin (BSA) and lignin were used to investigate the role of the acid-alcohol-enhanced Mannich reaction in nitrogen migration. The results showed that the acid-alcohol mixture could inhibit nitrogen enrichment in solids and the order of the denitrification rate was acetic acid > oxalic acid > citric acid. Acetic acid promoted solid-N hydrolysis to NH while oxalic acid preferred to convert it to oil-N. More tertiary amines and phenols were generated with oxalic acid-ethanol addition and then formed quaternary-N and N-containing aromatic compounds through the Mannich reaction. In the citric acid-ethanol-water solution, NH and amino acids were captured to form diazoxide derivatives in oil and pyrroles in solids through both nucleophilic substitution and the Mannich reaction. The results are able to guide biomass hydrochar production with the targeted regulation of nitrogen content and species.
Topics: Lignin; Carbon; Serum Albumin, Bovine; Nitrogen; Temperature; Ethanol; Biomass; Oxalates
PubMed: 37298884
DOI: 10.3390/molecules28114408 -
Alcohol (Fayetteville, N.Y.) Dec 2023The leukotrienes, lipid mediators, have a role in gastric damage induced by ethanol. Here, the gastroprotective effect of montelukast, an antagonist of the leukotriene...
The leukotrienes, lipid mediators, have a role in gastric damage induced by ethanol. Here, the gastroprotective effect of montelukast, an antagonist of the leukotriene receptor, and the involvement of the NO-cGMP-K channel pathway, were evaluated in gastric damage induced by ethanol in rats. For this, l-arginine, l-NAME, methylene blue (guanylate cyclase inhibitor), sildenafil, diazoxide, or glibenclamide (ATP-sensitive potassium channel blocker) were administered 30 min before montelukast (0.1, 1, 10, and 20 mg/kg, by mouth [p.o.]). After 1 h, to induce gastric damage, the rats received absolute ethanol (4 mL/kg, p.o.), and then microscopic, macroscopic, and pro-inflammatory parameters (TNF-α and IL-1β) were assessed. Results obtained here revealed that montelukast significantly attenuated the macroscopic and microscopic lesions induced by ethanol. Montelukast also reduced IL-1β and TNF-α levels. It was also observed that NOS inhibitor (l-NAME), methylene blue, and glibenclamide inhibited the effects of montelukast in the stomach. Moreover, the NO precursor (l-arginine), the PDE-5 inhibitor (sildenafil), and a potassium channel opener (diazoxide) before montelukast produced gastroprotective effects. In conclusion, the effect of montelukast against gastric lesions induced by ethanol is mediated, at least in part, through the pathway of the NO-cGMP-K channel.
Topics: Rats; Animals; NG-Nitroarginine Methyl Ester; Nitric Oxide; Sildenafil Citrate; Methylene Blue; Ethanol; Cyclic GMP; Glyburide; Tumor Necrosis Factor-alpha; Diazoxide; KATP Channels; Stomach; Arginine; Adenosine Triphosphate
PubMed: 37295565
DOI: 10.1016/j.alcohol.2023.05.008 -
BioRxiv : the Preprint Server For... May 2023Chronic pain is a substantial health burden and options for treating chronic pain remain minimally effective. Ketogenic diets are emerging as well-tolerated, effective...
Chronic pain is a substantial health burden and options for treating chronic pain remain minimally effective. Ketogenic diets are emerging as well-tolerated, effective therapeutic strategies in preclinical models of chronic pain, especially diabetic neuropathy. We tested whether a ketogenic diet is antinociceptive through ketone oxidation and related activation of ATP-gated potassium (K) channels in mice. We demonstrate that consumption of a ketogenic diet for one week reduced evoked nocifensive behaviors (licking, biting, lifting) following intraplantar injection of different noxious stimuli (methylglyoxal, cinnamaldehyde, capsaicin, or Yoda1) in mice. A ketogenic diet also decreased the expression of p-ERK, an indicator of neuronal activation in the spinal cord, following peripheral administration of these stimuli. Using a genetic mouse model with deficient ketone oxidation in peripheral sensory neurons, we demonstrate that protection against methylglyoxal-induced nociception by a ketogenic diet partially depends on ketone oxidation by peripheral neurons. Injection of tolbutamide, a K channel antagonist, prevented ketogenic diet-mediated antinociception following intraplantar capsaicin injection. Tolbutamide also restored the expression of spinal activation markers in ketogenic diet-fed, capsaicin-injected mice. Moreover, activation of K channels with the K channel agonist diazoxide reduced pain-like behaviors in capsaicin-injected, chow-fed mice, similar to the effects observed with a ketogenic diet. Diazoxide also reduced the number of p-ERK cells in capsaicin-injected mice. These data support a mechanism that includes neuronal ketone oxidation and activation of K channels to provide ketogenic diet-related analgesia. This study also identifies K channels as a new target to mimic the antinociceptive effects of a ketogenic diet.
PubMed: 37292762
DOI: 10.1101/2023.05.22.541799 -
Clinical Case Reports Jun 2023Kabuki syndrome is a congenital condition characterized by a set of facial dysmorphic features that often help the clinician to suspect the diagnosis. However, more...
Kabuki syndrome is a congenital condition characterized by a set of facial dysmorphic features that often help the clinician to suspect the diagnosis. However, more insidious symptoms can rarely occur, such as manifestations of hypoglycemia in newborns with congenital hyperinsulinism hypoglycemia, especially when a variant of the gene is found. In those cases, a treatment with diazoxide can be started and can be replaced with lanreotide if a satisfying glycemic control is not achieved. We report the case of a female patient born at 37 weeks of gestational age, without any obvious facial dysmorphic features, after a non-complicated pregnancy, that presented with feeding difficulties, drowsiness, and irritability revealing a hyperinsulinemic hypoglycemia. Further testing at 6 months old found a mutation. The patient was initially treated by diazoxide alone, but its dosage had to be lowered because of the occurrence of treatment side effects, and lanreotide had been added to maintain acceptable blood sugar levels. A congenital hyperinsulinemia hypoglycemia revealed heterozygous truncating variant in the gene, also known as X-linked Kabuki syndrome in a newborn. In cases of neonatal hypoglycemia, the first-line therapy is diazoxide. Our report shows that analogues of somatostatin such as lanreotide should be considered if the diazoxide regimen is not tolerated.
PubMed: 37257167
DOI: 10.1002/ccr3.7336 -
Journal of Pediatric Endocrinology &... Aug 2023CHI is a relevant cause of persistent and severe hypoglycemia and the ABCC8 gene mutation is one of most common cause of the disease. Two main types of CHI have been...
OBJECTIVES
CHI is a relevant cause of persistent and severe hypoglycemia and the ABCC8 gene mutation is one of most common cause of the disease. Two main types of CHI have been described, diffuse and focal form. Octreotide is a medication utilized in case of diazoxide-unresponsive forms of CHI. For those CHI focal forms where is decided either to manage medically or until resolutive surgery is completed, octreotide can be administered as subcutaneous injection or as continuous subcutaneous infusion via insulin pump. However, it is unclear how to adjust the drug's daily basal pattern when a pump is used.
CASE PRESENTATION
We present a case of an infant with a diazoxide-unresponsive focal form of CHI, due to ABCC8 mutation ABCC8, treated with octreotide. To better evaluate the glycemic trend, a CGM was placed. In order to achieve a better personalization of the therapy we utilized an insulin pump for octreotide administration.
CONCLUSIONS
The adoption of the CGM and insulin pump, allowed a better personalization of the therapy and a reduction of acute carbohydrate intake, promoting a good auxological growth before resolutive surgery. What is new? Octreotide administered with an insulin pump in patient with CHI allows a wide modulation of the daily therapy. The CGM allows a continuous and a less painful control of the glycemic trend in a patient with CHI. Different basal rates, given via insulin pump may allow a better personalization of the therapy. Prevention of hypoglycemia reduces the acute introduction of carbohydrates, promoting normal growth..
Topics: Humans; Male; Infant; Congenital Hyperinsulinism; Diazoxide; Octreotide; Blood Glucose Self-Monitoring; Treatment Outcome; Insulin
PubMed: 37248699
DOI: 10.1515/jpem-2022-0643 -
Frontiers in Endocrinology 2023Insulinomas, with an incidence of 4 cases per million individuals per year, remain amongst the most frequent functional neuroendocrine tumors. The usual diameter of...
Insulinomas, with an incidence of 4 cases per million individuals per year, remain amongst the most frequent functional neuroendocrine tumors. The usual diameter of insulinomas usually remains under 3 cm of major axis. However, 44 exceptional cases of "giant insulinomas", have been reported worldwide, generally exceeding 9 cm in major axis. In this article, we report the case of a 38-year-old woman whom suffered from chronic hypoglycemia despite treatment with diazoxide. Abdominal CT-scan revealed a 88 x 73 mm mass located at the tail of the pancreas. Following surgical excision, histopathological analysis confirmed G1 neuroendocrine tumor, with focal cytoplasmic expression of insulin in tumor cells. After a 16-month follow-up period, the patient didn't address any specific complaint, and no disease recurrence and/or metastasis were observed. A Ga-DOTATATE-PET scan was performed 6 months after surgery, which came back normal. Genetic evaluation has not been performed in our patient. The physiopathology of giant insulinomas remain unexplained, however with possible relationship with type 1 multiple endocrine neoplasia, sporadic somatic mutations and possible transformation of bulky non-functional pancreatic neuroendocrine tumors to a functional phenotype, with slow insulin secretion. While giant insulinomas remain rare in the literature, multicentric genetic analysis of tumor samples might reveal unique features of this rare subtype of neuroendocrine pancreatic tumors. Insulinomas of large size tend to have greater malignancy and higher rates of invasiveness. Careful follow-up, especially for liver and lymph node metastases, must be performed using functional imaging techniques to avoid disease relapse.
Topics: Humans; Insulinoma; Neoplasm Recurrence, Local; Pancreatic Neoplasms; Hypoglycemia; Neuroendocrine Tumors
PubMed: 37234805
DOI: 10.3389/fendo.2023.1125772 -
Annals of Medicine and Surgery (2012) May 2023Nonislet cell tumor hypoglycemia (NICTH) is a rare cause of hypoglycemia. It results from the secretion of insulin-like growth factor 2 from various tumors, which acts...
UNLABELLED
Nonislet cell tumor hypoglycemia (NICTH) is a rare cause of hypoglycemia. It results from the secretion of insulin-like growth factor 2 from various tumors, which acts on insulin receptors, increasing glucose utilization by the tumor. Among the treatment options for patients with NICTH, steroids have the best palliative effects.
CASE PRESENTATION
The authors present the case of a man with metastatic lung cancer who had multiple hospitalizations for hypoglycemia and associated anorexia, weight loss, and depression. After receiving steroids, the patient's hospital admission rate due to hypoglycemia reduced, depression improved, and weight loss reversed.
CLINICAL DISCUSSION
Steroids, diazoxide, octreotide, glucagon infusion, and recombinant growth hormone have shown good results in treating NICTH. Steroids have many advantages: they are easy to administer and relatively inexpensive. In our patient, steroids had the added benefit of improving the appetite with subsequent weight gain and controlling depression. They also significantly reduced the readmission rate.
CONCLUSION
NICTH is a rare cause of hypoglycemia. Glucocorticoids show better palliative effects than other medical treatments. In our patient, steroids dramatically reduced the number of hospitalizations due to hypoglycemia while improving the appetite, weight, and depression.
PubMed: 37228993
DOI: 10.1097/MS9.0000000000000537 -
Pediatrics and Neonatology Sep 2023
Topics: Humans; Infant; Diazoxide; Trichlormethiazide; Trisomy 13 Syndrome; Body Water; Treatment Outcome
PubMed: 37225554
DOI: 10.1016/j.pedneo.2023.04.003 -
Journal of Neurophysiology Jun 2023Inhibition of glycolysis with 2-deoxyglucose (2-DG) produces antiseizure effects in brain slices and animal models, yet the mechanisms remain elusive. Here, we examined...
Inhibition of glycolysis with 2-deoxyglucose (2-DG) produces antiseizure effects in brain slices and animal models, yet the mechanisms remain elusive. Here, we examined two glycolysis-derived ATP-associated mechanisms: vacuole ATP pump (V-ATPase) and ATP-sensitive K channel (K). Epileptiform bursts were generated in the CA3 area of hippocampal slices by 0 Mg and 4-aminopyridine. 2-DG consistently abolished epileptiform bursts in the presence of pyruvate (to sustain tricarboxylic acid cycle for oxidative ATP production) at 30-33°C but not at room temperature (22°C). Under physiological conditions, 2-DG did not reduce the amplitude of evoked excitatory postsynaptic currents (EPSCs) or the paired-pulse ratio in CA3 neurons. During repetitive high-frequency (20 Hz, 20-50 pulses) stimulation, 2-DG did not accelerate the decline of EPSCs (i.e., depletion of transmitter release), even when preincubated with 8 mM K to enhance activity-dependent uptake of 2-DG. In addition, in 2-DG tetanic stimulation (200 Hz, 1 s) dramatically increased rather than diminished the occurrence of spontaneous EPSCs immediately after stimulation (i.e., no transmitter depletion). Moreover, a V-ATPase blocker (concanamycin) failed to block epileptiform bursts that were subsequently abolished by 2-DG. Furthermore, 2-DG did not induce detectable K current in hippocampal neurons. Finally, epileptiform bursts were not affected by either a K opener (diazoxide) or a K blocker (glibenclamide) but were blocked by 2-DG in the same slices. Altogether, these data suggest that 2-DG's antiseizure action is temperature dependent and achieved exclusively by inhibition of glycolysis and is not likely to be mediated by the two membrane-bound ATP-associated machinery mechanisms, V-ATPase and K Inhibition of glycolysis with 2-deoxyglucose (2-DG) represents a novel metabolic antiseizure approach, yet the mechanisms remain elusive. Here, we show that 2-DG's antiseizure action is both glycolysis and temperature dependent but not mediated by the vacuole ATP pump (V-ATPase) or ATP-sensitive K channel (K) Our data provide new insights to understand 2-DG's cellular mechanisms of action and, more broadly, neuronal metabolism and excitability.
Topics: Animals; Deoxyglucose; Vacuoles; Hippocampus; Adenosine Triphosphatases; Adenosine Triphosphate
PubMed: 37222440
DOI: 10.1152/jn.00124.2023 -
Endocrinology, Diabetes & Metabolism... May 2023Neonatal hypoglycemia is a serious condition that can have a major impact on the growing neonatal brain. The differential diagnosis of neonatal hypoglycemia is broad and...
SUMMARY
Neonatal hypoglycemia is a serious condition that can have a major impact on the growing neonatal brain. The differential diagnosis of neonatal hypoglycemia is broad and includes hyperinsulinism as well as panhypopituitarism. The FOXA2 gene has been involved in the development of the pancreas as well as the pituitary gland. Six cases have been reported thus far with FOXA2 mutations presenting with variable degrees of hypopituitarism, and only two patients had permanent hyperinsulinism; other cases have been reported with microdeletions in 20p11, the location that encompasses FOXA2, and those patients presented with a wider phenotype. A full-term female infant presented with severe hypoglycemia. Critical sampling showed an insulin of 1 mIU/mL, suppressed beta-hydroxybutyric acids, and suppressed free fatty acids. Blood glucose responded to glucagon administration. Growth hormone (GH) stimulation test later showed undetectable GH in all samples, and cortisol failed to respond appropriately to stimulation. Gonadotropins were undetectable at 1 month of life, and MRI showed ectopic posterior pituitary, interrupted stalk, hypoplastic anterior pituitary, cavum septum pellucidum, and diminutive appearance of optic nerves. Whole-exome sequencing revealed a likely pathogenic de novo c.604 T>C, p.Tyr202His FOXA2 mutation. We expand the known phenotype on FOXA2 mutations and report a likely pathogenic, novel mutation associated with hyperinsulinism and panhypopituitarism.
LEARNING POINTS
FOXA2 has been shown to play an important role in the neuroectodermal and endodermal development. FOXA2 mutation may lead to the rare combination of hyperinsulinism and panhypopituitarism. Patients reported so far all responded well to diazoxide. Dysmorphology may be subtle, and liver functions should be monitored.
PubMed: 37219505
DOI: 10.1530/EDM-22-0355