Effect of dexmedetomidine on cardiorespiratory regulation in spontaneously breathing adult rats

Purpose We examined the cardiorespiratory effect of dexmedetomidine, an α2- adrenoceptor/imidazoline 1 (I1) receptor agonist, in spontaneously breathing adult rats. Methods Male rats (226−301 g, n = 49) under isoflurane anesthesia had their tail vein cannulated for drug administration and their tail artery cannulated for analysis of mean arterial pressure (MAP), pulse rate (PR), and arterial blood gases (PaO2, PaCO2, pH). After recovery, one set of rats received normal saline for control recording and was then divided into three experimental groups, two receiving dexmedetomidine (5 or 50 μg·kg−1) and one receiving normal saline (n = 7 per group). Another set of rats was divided into four groups receiving dexmedetomidine (50 μg·kg−1) followed 5 min later by 0.5 or 1 mg∙kg−1 atipamezole (selective α2-adrenoceptor antagonist) or efaroxan (α2-adrenoceptor/I1 receptor antagonist) (n = 6 or 8 per group). Recordings were performed 15 min after normal saline or dexmedetomidine administration. Results Compared with normal saline, dexmedetomidine (5 and 50 μg·kg−1) decreased respiratory frequency (fR, p = 0.04 and < 0.01, respectively), PR (both p < 0.01), and PaO2 (p = 0.04 and < 0.01), and increased tidal volume (both p = 0.049). Dexmedetomidine at 5 μg·kg−1 did not significantly change minute ventilation (V′E) (p = 0.87) or MAP (p = 0.24), whereas dexmedetomidine at 50 μg·kg−1 significantly decreased V′E (p = 0.03) and increased MAP (p < 0.01). Only dexmedetomidine at 50 μg·kg−1 increased PaCO2 (p < 0.01). Dexmedetomidine (5 and 50 μg·kg−1) significantly increased blood glucose (p < 0.01), and dexmedetomidine at 50 μg·kg−1 increased hemoglobin (p = 0.04). Supplemental atipamezole or efaroxan administration similarly prevented the 50 μg·kg−1 dexmedetomidine-related cardiorespiratory changes. Principal conclusion These results suggest that dexmedetomidine-related hypoventilation and hypertension are observed simultaneously and occur predominantly through activation of α2-adrenoceptors, but not I1 receptors, in spontaneously breathing adult rats.

Iatrogenic operative hysteroscopic intravascular absorption syndrome: a recurring possibility!

Background Operative hysteroscopic intravascular absorption syndrome (OHIA) is the constellation of signs and symptoms due to fluid overload during hysteroscopic procedures. It can present with hyponatremia, deranged coagulation, pulmonary, and cerebral edema which are life-threatening issues. To our knowledge, this is the first reported case of recurrent OHIA syndrome which was managed uneventfully. Case presentation A 26-year-old American Society of Anesthesiologist (ASA) patient presented with primary infertility and prolonged, heavy menstruation. The abdominal and transvaginal ultrasound (USG) revealed a large posterior intramural fibroid of size 6.1 cm × 4.2 cm with submucosal intracavitary extension. She was planned for two-step laparoscopic and hysteroscopic evaluation and resection of the myoma under general anesthesia. Severe OHIA syndrome occurred with 1.5% glycine in phase 1 resection and recurred with 0.9% sodium chloride in phase 2 resection of intrauterine myoma at two different surgical settings. The uniqueness of this case is recurrence of OHIA syndrome in the same patient despite the use of normal saline (NS) due to lack of precautionary measures for fluid management. Conclusions Normal saline as an irrigating medium may not eliminate the risk of OHIA. Lack of adequate fluid management strategies can be detrimental especially in cases of hysteroscopic myoma resections. Following a standard protocol for vigilant monitoring under general anesthesia is the key in successful management.

Balanced Crystalloid Versus Normal Saline as Resuscitative Fluid in Diabetic Ketoacidosis

Background: Large volume resuscitation with normal saline (NS) may be associated with iatrogenic hyperchloremia and renal injury. Objective: The purpose of this study was to assess clinical outcomes associated with the use of Lactated Ringer’s (LR) compared to NS as resuscitative fluid in diabetic ketoacidosis (DKA). Methods: Single-center, retrospective analysis of patients admitted for DKA. The primary objective of this study was to evaluate the incidence of iatrogenic hyperchloremia associated with fluid resuscitation using balanced crystalloid compared to NS. Results Iatrogenic hyperchloremia occurred more frequently in the NS group compared to the LR group (74.4% vs 64.2%; P = 0.05). Mean maximum serum chloride was higher in the NS group (115.7 mmol/L vs 113.7 mmol/L; P = 0.004). Incidence of hypernatremia was higher in the NS group (18.3% vs 9.3%; P = 0.02). There was no significant difference in the incidence of AKI; however, mean change in serum creatinine at 48 hours showed a significantly greater decrease in the LR group (-0.15 mg/dL vs -0.04 mg/dL; P = 0.002). No significant differences were found in intensive care unit (ICU) length of stay or total hospital length of stay. Conclusion and Relevance This study found a statistically significant reduction in the incidence of iatrogenic hyperchloremia with the use of LR compared to NS as fluid resuscitation in DKA. Serum creatinine was more improved in the LR group versus NS group at 48 hours. Preferential use of balanced crystalloid for fluid resuscitation in DKA may reduce incidence of hyperchloremia and support renal recovery in this population.

Clausena Harmandiana Root Extract Improved Amyloid-β Induced Cognitive Impairments in Rats By Reducing Aβ1-42 Protein Levels and Neuroinflammation

Background: Neuroinflammation caused by amyloid‐β (Aβ) is associated with Alzheimer’s disease (AD) pathogenesis. In AD, Aβ accumulation can activate the surrounding microglia which followed by the synthesis and release of pro-inflammatory cytokines, including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNFα), results in cognitive impairments. Clausena harmandiana (CH) is an herb in the Rutaceae family and has been used in folk medicine for the treatment of illness such as stomachache and headache, and as a health tonic. It is interesting that CH root extract (CHRE) exhibits various anti-inflammatory and other pharmacological activities, but there has not been any study in Alzheimer's disease-like animal models.Objectives: This study aimed to investigate the effects of CHRE on Aβ1-42-induced cognitive impairments, increased Aβ1-42 protein levels and neuroinflammation. Methods: Forty-eight adult male Sprague-Dawley rats (250-300 g) were randomly divided into 6 groups (n=8). The rats were given 0.5% sodium carboxymethylcellulose, Celebrex® (10 mg/kg BW) or CHRE (125, 250, and 500 mg/kg BW) and not given any treatment by oral gavage for 35 days. On day 21, all treated rats were injected with aggregated Aβ1-42 at a concentration of 1 µg/µl into both lateral ventricles (1 µl/side), while untreated rats were injected with sterilized normal saline. Ten days later, their recognition memory was assessed using the novel object recognition test. At the end of the experiment, all rats were euthanized by an overdose of thiopental sodium (120 mg/kg BW) and transcardial perfusion with 0.9% normal saline solution, to observe Aβ1-42 protein levels and the expression of inflammatory markers (CD11b-positive microglia, IL-1β, and TNFα) in the cerebral cortex and hippocampus.Results: The results indicated that pretreatment with CHRE at all doses improved impairment of short- and long-term recognition memory. In addition, CHRE significantly decreased Aβ1-42 protein levels and the expression of inflammatory markers in both brain regions as well as pretreatment with Celebrex®.Conclusions: This suggests that CHRE has a potential therapeutic effect against Aβ1-42-induced cognitive impairments by reducing Aβ1-42 protein levels and neuroinflammation.

Effect of Some Months on Follicles and Oocytes Recovered from Iraqi Ewes

The aim of the current study was to know the effect of season on the numbers of follicles and Oocytes recovered during Several months. 304 genital systems of Ewes were collected from Al-Fallujah abattoir/ Al-Fallujah, Al-Anbar province, during the period from 3, January 2021 to 1, July 2021. The samples were transported with Cool Box contained normal saline to the Reproductive Biotechnology Lab/Dept. of Surgery and Obstetrics / College of Vet. Medicine, University of Fallujah. The results showed that the total numbers of Oocytes with Cumulus cells recovered were 1037 oocytes. The results also showed a significant difference (P≤ 0.01) in the numbers of follicles between the right and the left ovaries. The numbers of follicles present at right ovaries were 776 in a percentage of (56.73%) from the total numbers where it was 592 follicles at the left ovaries in a percent of (43.27%) from the total numbers. It has been observed superiority of right ovary on the left ovary in the numbers of oocytes recovered, where it was 603 oocytes (58.15 %) from the right ovary and 434 oocytes (41.85 %) from the Left ovary. Also, the results showed a high Significant difference (P≤ 0.01) in the size of large and small follicles numbers. when the small follicles have large numbers. It has been also concluded from this study that there was a significant difference (P≤ 0.01) in the numbers of follicles and oocytes between the months of March and April as compared with other months.

Novel treatment for glance necrosis due to priapism; presentation and review of literature

Introduction: Glans necrosis in association with priapism is very rare and its appropriate treatment is not known. There is a secondary cause in most cases. Case description: We treated a 65-year-old man with priapism and glans necrosis using a closed shunt (Winter), continuous penile irrigation with normal saline, and heparin for 48 h and waited for the necrotic area to resolve spontaneously. The treatment outcome was much better compared to previous cases in whom open surgery, irrigation with pure normal saline, and/or resection of the necrotic area were performed. Conclusion: In cases with priapism and glans ischemia, we recommend treating the condition with continuous covernose irrigation with heparinized saline and avoiding open surgery.

Antioxidant effect of Arrabideae chica (crajiru) extract on oxidative stress in diabetic rats

Objective: This study aimed to investigate the effects of the antioxidant potential of Arrabideae chica (crajiru) extract on oxidative stress in diabetic rats. Methods: Adult Wistar rats (Rattus norvegicus), weighing 238±12g were divided into three groups of six rats each: CN normal untreated control; DIAB+NS diabetic rats treated with normal saline; and diabetic rats treated with crajiru extract, DIAB+CR. The CN and DIAB+NS groups (control groups) received normal saline solution (NS) orally (gavage); rats in the DIAB+CR group received crajiru extract (300 mg/kg) once a day by gavage for 6 weeks. Measurements of urea and creatinine in serum, and kidney tissue catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) were performed. The variables were assessed using the Tukey test, significance p<0.05. Results: All animals survived the experiments. In the CN group, compared with the DIAB+NS group, there was significant difference between the levels of glycemia on the second day of dosing and on the 10th day (p<0.05). No difference was observed on glycemia comparing the 2th and 10th day on the rats of group C+NS (p>0.05). Diabetic animals from DIAB+CR group had a significant reduction in glycemia on 10th day of treatment, comparing the 2nd day (p<0.05). There was a significant reduction in glycemia in the DIAB+CR group, comparing with the DIAB+NS group (p<0.05). There was an increase in urea and creatinine levels in rats DIAB+SN when compared to controls, C+SN (p<0.001). Rats from the DIAB+CR group had a significant reduction in urea and creatinine, compared to the DIAB+NS group (p<0.001). There were no significant differences in urea and creatinine comparing the C+NS and DIAB+CR groups. The rats from the DIAB+NS group had significantly lower levels of CAT, GSH-px and SOD when compared to the normal control rats (p<0.001). In animals from the DIAB+SN group, the levels of these antioxidant enzymes were significantly reduced (p<0.001). The treatment of diabetics with crajiru extract caused a significant increase (p<0.001) in the levels of CAT, GSH-px and SOD, when compared to rats in the BIAB+SN group. Conclusion: The data of the present study confirms that the crajiru extract positively influenced the control of hyperglycemia in diabetic rats. More research is needed to provide a better understanding of the mechanisms of diabetes treatment using crajiru extract and its flavonoids.

GnRH-a-Induced Perimenopausal Rat Modeling and Black Cohosh Preparations’ Effect on Rat’s Reproductive Endocrine

BackgroundEndometriosis (EMS) is an estrogen-dependent disease, which easily recurs after operation. Gonadotropin-releasing hormone agonist (GnRH-a), an estrogen-inhibiting drug, can effectively inhibit the secretion of gonadotropin by pituitary gland, so as to significantly decrease the ovarian hormone level and facilitate the atrophy of ectopic endometrium, playing a positive role in preventing postoperative recurrence. The application of GnRH-a can lead to the secondary low estrogen symptoms, namely the perimenopausal symptoms, and is a main reason for patients to give up further treatment. The add-back therapy based on sex hormones can well address the perimenopausal symptoms, but long-term use of hormones may cause the recurrence of EMS, as well as liver function damage, venous embolism, breast cancer and other risks, which has long been a heated topic in the industry. Therefore, it is necessary to find effective and safe anti-additive drugs soon. Studies at home and abroad show that, as a plant extract, isopropanolic extract of cimicifuga racemosa (ICR) can well relieve the perimenopausal symptoms caused by natural menopause. Some studies have preliminarily confirmed that black cohosh preparations can antagonize perimenopausal symptoms of EMS patients treated with GnRH-a after operation.ObjectiveTo establish a rat model of perimenopausal symptoms induced by GnRH-a injection, for the purposes of laying a foundation for further research and preliminarily exploring the effect of black cohosh preparations on reproductive endocrine of the rat model.MethodThe rat model of perimenopausal symptoms was established by GnRH-a injection, and normal saline (NS injection) was used as the control. The rats were randomly divided into four groups according to different modeling methods and drug intervention schemes. GnRH-a injection + normal saline intervention group (GnRH-a + NS), normal saline injection control + normal saline intervention group (NS + NS), GnRH-a injection + estradiol intervention group (GnRH-a + E2), and GnRH-a injection + black cohosh preparations intervention group (GnRH-a + ICR). After modelling was assessed to be successful with the vaginal smear method, the corresponding drugs were given for intervention for 28d. In the process of rat modeling and drug intervention, the skin temperature and anus temperature of the rat tails were measured every other day, the body weights of the rats were measured every other day, and the dosage was adjusted according to the body weight. After the intervention was over, the serum sex hormone level, the uterine weight, the uterine index, and the endometrial histomorphology changes, as well as the ovarian weight, the ovarian index, and the morphological changes of ovarian tissues of each group were measured.Results(1) The vaginal cell smears of the control group (NS + NS) showed estrous cycle changes, while other model rats had no estrous cycle of vaginal cells. (2) The body weight gains of the GnRH-a + NS, GnRH-a + E2 and GnRH-a + ICR groups were significantly higher than that of the NS + NS control group. The intervention with E2 and ICR could delay the weight gain trend of rats induced by GnRH-A. (3) After GnRH-a injection, the temperature of the tail and anus of rats showed an overall upward trend, and the intervention with E2 and ICR could effectively improve such temperature change. (4) The E2, FSH, and LH levels in the GnRH-a + NS, GnRH-a + E2, and GnRH-a + ICR groups were significantly lower than those in the NS + NS group (P &lt; 0.01). The E2 level was significantly higher and the LH level was significantly lower in the GnRH-a + E2 group than those in the GnRH-a + NS and GnRH-a + ICR groups (P &lt; 0.05). Compared with those of the GnRH-a + NS and GnRH-a + ICR groups, the FSH level of the GnRH-a + E2 group showed a slight downward trend, but the difference was not statistically significant (P &gt; 0.05). There was no significant difference in the levels of sex hormones between the GnRH-a + NS group and GnRH-a + ICR group (P &gt; 0.05). (5) Compared with those of the NS + NS group, the uterine weight and uterine index of the GnRH-a + NS, GnRH-a + E2 and GnRH-a + ICR groups significantly decreased (P &lt; 0.01). In a comparison between the groups, the uterine weight and uterine index in the GnRH-a + NS and GnRH-a + ICR groups were significantly lower than those in the GnRH-a + E2 group (P &lt; 0.01). There was a statistical difference in the uterine weight and uterine index between the GnRH-a + NS group and GnRH-a + ICR group (P &gt; 0.05). (6) Compared with those of the NS + NS group, the ovarian weight and ovarian index of the GnRH-a + NS, GnRH-a + E2 and GnRH-a + ICR groups significantly decreased (P &lt; 0.01). There was no statistical difference in the ovarian weight and ovarian index among the GnRH-a + E2, GnRH-a + NS and GnRH-a + ICR groups (P &gt; 0.05). (7) Compared with those in the NS + NS group, the number of primordial follicles increased significantly, while the number of growing follicles and mature follicles decreased significantly in the GnRH-a + NS, GnRH-a + E2, and GnRH-a + ICR groups (P &lt; 0.01), but there was a statistical difference in the total number of follicles among the four groups (P &gt; 0.05).ConclusionsThe GnRH-a injection could achieve the desired effect. The animal model successfully achieved a significant decrease in the E2, FSH, and LH levels in rats, and could cause the rats to have rising body surface temperature similar to hot flashes in the perimenopausal period. The intervention with E2 and ICR could effectively relieve such “perimenopausal symptoms”, and ICR had no obvious effect on the serum sex hormone level in rats.

Hypoglycaemic Activity of Extra Virgin Avocado (Persea americana) Oil and Extra Virgin Coconut (Cocos nucifera) Oil on Alloxan-induced Diabetic Rats

Diabetes mellitus is a chronic, metabolic disorder characterized by abnormal elevation of blood glucose levels (hyperglycaemia). Despite significant milestones achieved using conventional drugs in managing the disease, there are some drawbacks associated with their use such as drug resistance, adverse drug effects, high cost, and sometimes outright therapeutic failure. The urgent need to bridge this therapeutic lacuna calls for further exploration and investigation of other treatment options. This study therefore aims at evaluating the antidiabetic potentials of virgin avocado oil and virgin coconut oil in alloxan-induced diabetic rats. Animals were divided into 5 groups of five rats each. Group 1 (negative control) received 10 ml /kg/day of normal saline, group 2 (diabetic control) -10 ml/kg/day of normal saline; group 3 received extra virgin avocado oil (1 ml/250 g) body weight, group 4 received extra virgin coconut oil (2 ml/kg) bodyweight, and group 5 received 10 mg/kg/day of metformin. Treatments were administered orally for 15 days. Extra virgin avocado oil and extra virgin coconut oil respectively showed significant antidiabetic activities, and may be beneficial for management of diabetes mellitus.