Effects of intrarenal angiotensin 1-7 infusion on renal haemodynamic and excretory function in anaesthetised two-kidney one-clip and deoxycorticosterone acetate-salt hypertensive rats.

NEW FINDINGS: What is the central question of this study? Are renal functional responses to intrarenal angiotensin 1-7 (Ang (1-7)) infusion dependent on the level of the endogenous renin-angiotensin system (RAS) in the two-kidney one-clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt animal models of hypertension? What is the main finding and its importance? The renal actions of Ang (1-7) are dependent on the relative endogenous levels of each arm of the classical angiotensin II-angiotensin II type 1 receptor (AT1 R) axis and those of the Ang (1-7)-Mas receptor axis. These findings support the hypothesis that a balance exists between the intrarenal classical and novel arms of the RAS, and in particular the relative abundance of AT1 R to Mas receptor, which may to a large extent determine the renal excretory response to Ang (1-7) infusion. ABSTRACT: This study investigated the action of angiotensin 1-7 (Ang (1-7)) on renal haemodynamic and excretory function in the two-kidney one-clip (2K1C) and deoxycorticosterone acetate (DOCA)-salt rat models of hypertension, in which the endogenous renin-angiotensin system (RAS) activity was likely to be raised or lowered, respectively. Rats were anaesthetised and prepared for the measurement of mean arterial pressure and kidney function during renal interstitial infusion of Ang (1-7) or saline. Kidney tissue concentrations of angiotensin II (Ang II) and Ang (1-7) were determined. Intrarenal infusion of Ang (1-7) into the clipped kidney of 2K1C rats increased urine flow (UV), absolute (UNa V) and fractional sodium (FENa ) excretions by 110%, 214% and 147%, respectively. Renal Ang II concentrations of the clipped kidney were increased with no major changes in Ang (1-7) concentration. By contrast, Ang (1-7) infusion decreased UV, UNa V, and FENa by 27%, 24% and 21%, respectively in the non-clipped kidney in which tissue Ang (1-7) concentrations were increased, but renal Ang II concentrations were unchanged compared to sham animals. Ang (1-7) infusion in DOCA-salt rats had minimal effects on glomerular filtration rate but significantly decreased UV, UNa V and FENa by ∼30%. Renal Ang (1-7) concentrations were higher and Ang II concentrations were lower in DOCA-salt rats compared to sham rats. These findings demonstrate that the intrarenal infusion of exogenous Ang (1-7) elicits different renal excretory responses the magnitude of which is dependent on the balance between the endogenous renal Ang II-AT1 receptor axis and Ang (1-7)-Mas receptor axis.

An investigation of preclinical medical students' preference for summative or formative assessment for physiology learning.

Both summative and formative assessments are known to facilitate student learning and understanding and help students to identify areas of weakness. However, few studies have investigated students' preference for either summative or formative evaluations, particularly in the area of preclinical medicine. The current study addresses this deficit by surveying 137 first-year graduate entry to medicine (GEM) preclinical medical students from 2 consecutive years (2018-2019 and 2019-2020), for their thoughts on the 6 summative (i.e., for a small percentage of marks), proctored and the 5 informal, formative (i.e., no marks available) continuous assessments in physiology that they encountered in semesters 1 and 2, respectively. Our survey revealed that between 75 and 90% of students felt that both evaluation formats were roughly equally useful (i.e., selecting options, "agree" or "strongly agree") both for providing feedback about their understanding of physiology and for identifying deficits in their physiology knowledge. However, although a significantly larger number of students felt that summative evaluations motivated them to study more than the formative evaluations (P = 0.006), overall, more students favored formative over summative assessments. Notably, however, GEM students from nonbiomedical backgrounds were significantly more in favor of summative assessments than those from either biomedical backgrounds (P = 0.003) or the whole GEM survey cohort (P = 0.01). The implications of these findings will be discussed, with suggestions as to how the student views outlined here might be facilitated within an academic program to maximize both student learning as well as their motivation to study and keep up with taught material.NEW & NOTEWORTHY Although several studies have investigated the relative effectiveness of regular summative versus formative assessments as tools to facilitate student learning and understanding, ours is the first to explicitly solicit students' views on, and preferences for, either regular formative or summative assessment in preclinical medicine. We demonstrate that, overall, students preferred formative- to summative-type assessments, due to the immediacy of feedback, but also that summative tests incentivized them to study and keep up with material more.

Appendiceal involvement in pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a diagnostic challenge in the coronavirus disease (COVID) era.

BACKGROUND: Many studies on pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS) have described abdominal findings as part of multisystem involvement, with limited descriptions of abdominal imaging findings specific to PIMS-TS. OBJECTIVE: To perform a detailed evaluation of abdominal imaging findings in children with PIMS-TS. MATERIALS AND METHODS: We performed a single-center retrospective study of children admitted to our institution between April 2020 and January 2021 who fulfilled Royal College of Paediatrics and Child Health criteria for PIMS-TS and who had cross-sectional abdominal imaging. We studied clinical data, abdominal imaging, laboratory markers, echocardiography findings, treatment and outcomes for these children. We also reviewed the literature on similar studies. RESULTS: During the study period, 60 PIMS-TS cases were admitted, of whom 23 required abdominal imaging. Most (74%) were from a Black, Asian or minority ethnic background and they had an average age of 7 years (range 2-14 years). All children had fever and gastrointestinal symptoms on presentation with elevated C-reactive protein, D-dimer and fibrinogen. Most had lymphopenia, raised ferritin and hypoalbuminemia, with positive severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies in 65%. Free fluid (78%), right iliac fossa mesenteric inflammation (52%), and significantly enlarged mesenteric lymph nodes (52%) were the most common imaging findings. Appendiceal inflammation (30%) and abnormal distal ileum and cecum/ascending colon wall thickening (35%) were also common. All children responded well to medical management alone, with no mortality. CONCLUSION: In addition to free fluid, prominent lymphadenopathy, and inflammatory changes in the right iliac fossa, we found abnormal long-segment ileal thickening and appendicitis to be frequent findings. Recognition of appendiceal involvement as a component of the PIMS-TS spectrum should help clinicians avoid unnecessary surgical intervention as part of a multidisciplinary team approach.

Chronic intermittent hypoxia impairs diuretic and natriuretic responses to volume expansion in rats with preserved low-pressure baroreflex control of the kidney.

We examined the effects of exposure to chronic intermittent hypoxia (CIH) on baroreflex control of renal sympathetic nerve activity (RSNA) and renal excretory responses to volume expansion (VE) before and after intrarenal transient receptor potential vanilloid 1 (TRPV1) blockade by capsaizepine (CPZ). Male Wistar rats were exposed to 96 cycles of hypoxia per day for 14 days (CIH) or normoxia. Urine flow and absolute Na+ excretion during VE were less in CIH-exposed rats, but the progressive decrease in RSNA during VE was preserved. Assessment of the high-pressure baroreflex revealed an increase in the operating and response range of RSNA and decreased slope in CIH-exposed rats with substantial hypertension [+19 mmHg basal mean arterial pressure (MAP)] but not in a second cohort with modest hypertension (+12 mmHg). Intrarenal CPZ caused diuresis, natriuresis, and a reduction in MAP in sham-exposed (sham) and CIH-exposed rats. After intrarenal CPZ, diuretic and natriuretic responses to VE in CIH-exposed rats were equivalent to those of sham rats. TRPV1 expression in the renal pelvic wall was similar in both experimental groups. Exposure to CIH did not elicit glomerular hypertrophy, renal inflammation, or oxidative stress. We conclude that exposure to CIH 1) does not impair the low-pressure baroreflex control of RSNA; 2) has modest effects on the high-pressure baroreflex control of RSNA, most likely indirectly due to hypertension; 3) can elicit hypertension in the absence of kidney injury; and 4) impairs diuretic and natriuretic responses to fluid overload. Our results suggest that exposure to CIH causes renal dysfunction, which may be relevant to obstructive sleep apnea.

The renal excretory responses to acute renal interstitial angiotensin (1-7) infusion in anaesthetised spontaneously hypertensive rats.

This study investigated the impact of intrarenal angiotensin 1-7 (Ang [1-7]) infusion on renal excretory function in a rat model of hypertension. Eleven-week-old spontaneously hypertensive rats (SHRs, n = 7) and Han Wistar controls (NCR, n = 7) were anaesthetised with sodium pentobarbital (60 mg/kg i.p.) and prepared for the measurement of mean arterial pressure (MAP) and left renal function during renal interstitial infusion of Ang (1-7) (50 ng/min). The kidneys were harvested, the renal cortex and medulla separated, prepared for measurement of Ang II and Ang (1-7) and Western blot determination of AT1 and Mas receptor protein expression. MAP, glomerular filtration rate (GFR), urine flow (UF) and absolute sodium excretion (UNaV) were 109 ± 16 mmHg, 4.4 ± 1.0 mL/min/kg, 102 ± 16 µL/min/kg and 16 ± 3 µmol/min/kg, respectively in the NCR and 172 ± 24 mmHg, 3.4 ± 0.7 mL/min/kg, 58 ± 30 µL/min/kg and 8.6 ± 4.8 µmol/min/kg respectively in the SHR. Ang (1-7) increased UF (31%), UNa V (50%) and fractional sodium excretion (FENa+ ) (22%) in the NCR group (all p < 0.05) but had no effect on GFR in either group. The magnitudes of the Ang (1-7)-induced increases in UF and UNa V were significantly blunted in the SHR group (model × drug p < 0.05). The renal cortical AT1: Mas receptor expression ratio was significantly higher in the SHR group (p < 0.05) but renal Ang II and Ang (1-7) levels were not statistically different between groups. The Ang (1-7)-induced increases in sodium and water excretion were impaired in the SHR group in the context of an unstimulated RAS. The decrease in responsiveness of the SHR kidney to Ang (1-7) appears to be associated with higher levels of AT1 receptor expression in the renal cortex.

Effects of intracerebroventricular leptin and orexin-A on the baroreflex control of renal sympathetic nerve activity in conscious rats fed a normal or high-fat diet.

This study examined the effect of leptin and orexin-A on autonomic baroreflex control in conscious Wistar rats exposed to high-fat (45% fat) or normal (3.4%) diet for 4 weeks. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored during the generation of baroreflex gain curves and acute volume expansion (VEP). Intracerebroventricular (ICV) leptin (1 µg/min) increased RSNA in the normal diet group (0.31 ± 0.04 vs 0.23 ± 0.03 mV/s) and MAP in the high-fat diet group (115 ± 5 vs 105 ± 5 mm Hg, P < .05). Orexin-A (50 ng/min) increased RSNA, HR and MAP in the high-fat diet group (0.26 ± 0.03 vs 0.22 ± 0.02 mV/s, 454 ± 8 vs 417 ± 12 beats/min, 117 ± 1 vs 108 ± 1 mm Hg) and the normal diet group (0.18 ± 0.05 vs 0.17 ± 0.05 mV/s, 465 ± 10 vs 426 ± 6 beats/min, 116 ± 2 vs 104 ± 3 mm Hg). Baroreflex sensitivity for RSNA was increased during ICV leptin by 50% in the normal diet group, compared to 14% in the high-fat diet group (P < .05). Similarly, orexin-A increased baroreflex sensitivity by 56% and 50% in the high-fat and normal diet groups, respectively (all P < .05). During ICV saline, VEP decreased RSNA by 31 ± 5% (P < .05) after 10 minutes and the magnitude of this response was blunted during ICV infusion of leptin (17 ± 2%, P < .05) but not orexin-A in the normal diet group. RSNA response to VEP was not changed during ICV leptin or orexin-A in the high-fat diet group. These findings indicate possible central roles for leptin and orexin-A in modulating the baroreflexes under normal or increased fat intake in conscious rats and potential therapeutic approaches for obesity associated hypertension.

A Narrative Review on the Phytochemistry, Pharmacology and Therapeutic Potentials of Clinacanthus nutans (Burm. f.) Lindau Leaves as an Alternative Source of Future Medicine.

The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant's extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this review paper compiles all the available contemporary data from this subtropical herb on its phytochemistry and pharmacological activities with a view towards garnering further interest in exploring its use in cardiovascular and renal diseases.

Renal cortical oxygen tension is decreased following exposure to long-term but not short-term intermittent hypoxia in the rat.

Chronic kidney disease (CKD) occurs in more than 50% of patients with obstructive sleep apnea (OSA). However, the impact of intermittent hypoxia (IH) on renal function and oxygen homeostasis is unclear. Male Sprague-Dawley rats were exposed to IH (270 s at 21% O2; 90 s hypoxia, 6.5% O2 at nadir) for 4 h [acute IH (AIH)] or to chronic IH (CIH) for 8 h/day for 2 wk. Animals were anesthetized and surgically prepared for the measurement of mean arterial pressure (MAP), and left renal excretory function, renal blood flow (RBF), and renal oxygen tension (Po2). AIH had no effect on MAP (123 ± 14 vs. 129 ± 14 mmHg, means ± SE, sham vs. IH). The CIH group was hypertensive (122 ± 9 vs. 144 ± 15 mmHg, P < 0.05). Glomerular filtration rate (GFR) (0.92 ± 0.27 vs. 1.33 ± 0.33 ml/min), RBF (3.8 ± 1.5 vs. 7.2 ± 2.4 ml/min), and transported sodium (TNa) (132 ± 39 vs. 201 ± 47 µmol/min) were increased in the AIH group (all P < 0.05). In the CIH group, GFR (1.25 ± 0.28 vs. 0.86 ± 0.28 ml/min, P < 0.05) and TNa (160 ± 39 vs. 120 ± 40 µmol/min, P < 0.05) were decreased, while RBF (4.13 ± 1.5 vs. 3.08 ± 1.5 ml/min) was not significantly different. Oxygen consumption (QO2) was increased in the AIH group (6.76 ± 2.60 vs. 13.60 ± 7.77 µmol/min, P < 0.05), but it was not significantly altered in the CIH group (3.97 ± 2.63 vs. 6.82 ± 3.29 µmol/min). Cortical Po2 was not significantly different in the AIH group (46 ± 4 vs. 46 ± 3 mmHg), but it was decreased in the CIH group (44 ± 5 mmHg vs. 38 ± 2 mmHg, P < 0.05). For AIH, renal oxygen homeostasis was preserved through a maintained balance between O2 supply (RBF) and consumption (GFR). For CIH, mismatched TNa and QO2 reflect inefficient O2 utilization and, thereby, sustained decrease in cortical Po2.

Tacrolimus restores the high- and low-pressure baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal injury rats.

NEW FINDINGS: What is the central question of this study? Does immunosuppression restore the baroreflex control of renal sympathetic nerve activity (RSNA) in an animal model of kidney injury? What is the main finding and its importance? Tacrolimus, a calcineurin inhibitor, restored the high- and low-pressure baroreflex control of RSNA following cisplatin-induced renal injury. ABSTRACT: Cisplatin administration causes depression of renal haemodynamic and excretory function and is associated with renal sympatho-excitation and loss of baroreflex regulation of renal sympathetic nerve activity (RSNA). This study investigated whether administration of the immunosuppressant tacrolimus in this cisplatin-mediated renal injury model could restore, or the acute intra-renal infusion of tumour necrosis factor α (TNF-α) could blunt, the high- or low-pressure baroreflex control of RSNA. Groups of control and cisplatin-treated (5 mg kg-1 , i.p. on day 0) rats received either saline or tacrolimus (0.25 mg kg-1  day-1 , i.p.) for 7 days prior to study. Rats were anaesthetised and prepared for measurement of mean arterial pressure (MAP), heart rate (HR) and RSNA. Baroreflex gain curves were generated and the degree of renal sympatho-inhibition determined (area under the curve (AUC) reported as %RSNA min) during acute volume expansion. Intrarenal TNF-α infusion (0.3 µg kg-1  h-1 ) in control rats decreased baroreflex gain by 32% (P < 0.05) compared to intra-renal saline infusion. In the cisplatin group (MAP: 98 ± 14 mmHg; HR: 391 ± 24beats min-1 ), the baroreflex gain for RSNA was 39% (P < 0.05) lower than that for the control group (MAP: 91 ± 7 mmHg; HR: 382 ± 29 beats min-1 ). In cisplatin-treated rats given daily tacrolimus (MAP: 84 ± 12 mmHg; HR: 357 ± 30 beats min-1 ), the baroreflex gain and renal sympatho-inhibition (AUC, 2440 ± 1071 vs. 635 ± 498% min) were restored to normal values. These findings provide evidence for the view that cisplatin administration initiates an injury involving inflammation which may contribute to the deranged baroreflex regulation of RSNA. This phenomenon appears mediated in part via the renal innervation.

Effect of pioglitazone on vasopressor responses to adrenergic agonists and angiotensin II in diabetic and non-diabetic spontaneously hypertensive rats.

Pioglitazone, peroxisome proliferator-activated receptor (PPAR-γ) agonist, is a therapeutic drug for diabetes. Present study investigated the interaction between PPAR-γ and alpha adrenoceptors in modulating vasopressor responses to Angiotensin II (Ang II) and adrenergic agonists, in diabetic & non-diabetic Spontaneously Hypertensive Rats (SHRs). Diabetes was induced with an i.p injection of streptozotocin (40 mg/kg) in two groups (STZ-CON, STZ-PIO), whereas two groups remained non diabetic (ND-CO, ND-PIO). One diabetic and non-diabetic group received Pioglitazone (10mg/kg) orally for 21 days. On day 28, the animals were anaesthetized with sodium pentobarbitone (60mg/kg) and prepared for measurement of systemic haemodynamics. Basal mean arterial pressure of STZ-CON was higher than ND-CON, whereas following pioglitazone treatment, MAP was lower compared to respective controls. MAP responses to i.v administration of NA, PE, ME and ANG II were significantly lower in diabetic SHRs: STZ-CON vs ND-CON (35%). Pioglitazone significantly decreased responses to NA, PE, ME and ANG II in ND-PIO versus ND-CON by 63%. Responses to NA and ANG II were significantly attenuated in STZ-PIO vs. ND-PIO (40%). PPAR-γ regulates systemic hemodynamic in diabetic model and cross-talk relationship exists between PPAR-γ and α1-adrenoceptors, ANG II in systemic vasculature of SHRs.

Assessment of renal function in the anaesthetised rat following injection of superparamagnetic iron oxide nanoparticles.

A recent study showed that a significant fall in mean arterial pressure (MAP) occurred following intravenous injection of two novel superparamagnetic iron oxide nanoparticles (SPIONs), MF66 and OD15. To assess if this was caused by excessive glomerular clearance, the effect of both particles on renal function was studied. Experiments were performed on sodium pentobarbital anaesthetised male Wistar rats (250-350 g). Twenty-minute urine clearances were taken followed by an i.v. bolus of MF66, OD15 (2 mg·kg-1), or dH2O (0.4 mL·kg-1). MF6 or OD15 injection resulted in a significant transient drop in MAP and renal blood flow by approximately 33% and 50% (P < 0.05). The absolute excretion of sodium was significantly increased (P < 0.05) by almost 80% and 70% following OD15 and MF66, respectively. Similarly, fractional excretion of sodium was increased by almost 80% and 60% following OD15 and MF66, respectively. The glomerular filtration rate was not significantly affected, but urine flow increased nonsignificantly by approximately 50% and 66% following i.v. injection of OD15 and MF66, respectively. SPIONs produce a decrease in blood pressure and a natriuresis; however, the rate of fluid filtration in the kidney was not significantly affected.

Effects of renal denervation on kidney function in patients with chronic kidney disease: a systematic review and meta-analysis.

The present study aims to evaluate the clinical outcomes following renal denervation (RDN) for hypertensive patients with chronic kidney disease (CKD). Prospective studies published between January 1, 2010 and November 15, 2022 where systematically identified for RDN outcomes on office and ambulatory blood pressure, estimated glomerular filtration rate (eGFR), creatinine and procedural characteristics from three online databases (Medline, PubMed, EMBASE). Random effects model to combine risk ratios and mean differences was used. Where possible, clinical outcomes were pooled and analyzed at 6, 12 and 24 months. Significance was set at p ≤ 0.05. 11 prospective trials, with a total of 226 patients with treatment resistant HTN receiving RDN met the inclusion criteria. Age ranged from 42.5 ± 13.8 to 66 ± 9. Main findings of this review included a reduction in systolic and diastolic office blood pressure at 6 [-19.8 (p < 0.00001)/-15.2 mm Hg (p < 0.00001)] and 12 months [-21.2 (p < 0.00001)/-9.86 mm Hg (p < 0.0005)] follow-up compared to baseline. This was also seen in systolic and diastolic 24-hour ambulatory blood pressure at 6 [-9.77 (p = 0.05)/-3.64 mm Hg (p = 0.09)] and 12 months [-13.42 (p = 0.0007)/-6.30 mm Hg (p = 0.001)] follow-up compared to baseline. The reduction in systolic and diastolic 24-hour ambulatory blood pressure was maintained to 24 months [(-16.30 (p = 0.0002)/-6.84 mm Hg (p = 0.0010)]. Analysis of kidney function through eGFR demonstrated non-significant results at 6 (+1.60 mL/min/1.73 m2, p = 0.55), 12 (+5.27 mL/min/1.73 m2, p = 0.17), and 24 months (+7.19 mL/min/1.73 m2, p = 0.36) suggesting an interruption in natural CKD progression. Similar results were seen in analysis of serum creatinine at 6 (+0.120 mg/dL, p = 0.41), 12 (+0.100 mg/dL, p = 0.70), and 24 months (+0.07 mg/dL, p = 0.88). Assessment of procedural complications deemed RDN in a CKD cohort to be safe with an overall complication rate of 4.86%. With the current advances in RDN and its utility in multiple chronic diseases beyond hypertension, the current study summarizes critical findings that further substantiate the literature regarding the potential of such an intervention to be incorporated as an effective treatment for resistant hypertension and CKD.

Effects of restraint stress and surface treatments on the stability of titanium dental implant osseointegration in dogs: An in vivo comparative study.

Objectives: This study was aimed at assessing the effects of restraint stress and sandblasting; sandblasting with acid etching; Er-Cr: YSGG laser treatment; and propolis coating of implant surfaces on the implant stability quotient (ISQ) of grade 4 titanium dental implant osseointegration in model dogs. Methods: A total of forty-eight CPTi dental implants were divided into four groups according to surface treatment: group A: sandblasting with acid etching; group B: sandblasting with Al2O3; group C: Er-Cr: YSGG laser; and group D: propolis coating. Sixteen male dogs of local breed,1-1.5 years of age, weighing 22 ± 3 kg, were divided into two main groups (n-8 dogs each): a non-stressed group (group I) and stressed group (group II). Each of these groups is further divided into four implant groups per surface treatment, A, B, C, and D (two dogs per implant group), each dog has three implants. The ISQ was tested at 0 (baseline), 14, and 90 days with a noninvasive EasyCheck® device. Serum cortisol in the stressed and non-stressed groups was analyzed at 0, 15, 30, 45, 60, 75, and 90 days with a canine cortisol ELISA kit. The data were statistically analyzed with one-way analysis of variance and Tukey's post hoc test at a 0.05 level of significance. Results: For implant stability quotient (ISQ), sandblasting in the non-stressed (group I) had the highest mean value (88.0) at 90-days, whereas sandblasting with acid etching at 14-days had the lowest mean value (82.6). Sandblasting in the stressed (group II) had the highest mean value (88.3) at 90-days, whereas the laser surface treatment had the lowest mean value (72.00) at 14-days. Serum cortisol (ng/µl) at 90 days (143.10 and 195.33 for non-stressed and stressed groups respectively), was significantly higher than other time intervals (P < 0.05). Conclusions: The ISQ was dependent on surface treatment, and was higher with sandblasting than the other treatments in the stressed and non-stressed groups at 90 days. For all surface-treated implants, the stressed group had significantly higher serum cortisol levels than the non-stressed group.

Radiographic and histologic assessment of osseointegration for surface-treated titanium dental implants: An experimental study in dogs.

Background: Modifying the dental implant's surface texture enhances its biological response to the bone and implant‒tissue interface, resulting in the successful support of forces. This study assessed the impact of sandblasting, sandblasting plus acid etching, Er,Cr:YSGG laser, and propolis implant surface treatments and occlusal load on the osseointegration of titanium dental implants in dogs. Methods: Seventy-two titanium dental implants with a diameter of 4 mm and a length of 10 mm were divided into four groups according to implant surface modifications (n=18 for each group): group A: sandblasting plus acid etching, group B: sandblasting with Al2 O3, group C: Er,Cr:YSGG laser, group D: propolis coating. Twenty-four local breed male dogs were used. Premolar teeth (P1, P2, and P3) were extracted on the left side of the mandible, and after 12 weeks of bone healing, implants were unilaterally installed. The osseointegration at three study times from implant installation (14, 90, and 180 days) was evaluated. The dog jaws were scanned using an intraoral scanner for the virtual design of screw-retained three-unit crowns after 90 days of osseointegration. Final radiographs were taken before the animals were sacrificed at 14, 90, and 180 days, and the histological analysis was performed. Results: Radiographic analysis showed new bone formation (NBF) along and in contact with the implant surface of the treated groups. The histological analysis after 14 days in groups A and B revealed a uniform and ongoing pattern of bone growth and many osteoblasts with few osteocytes within lacunae in new bone trabeculae. Group C showed an increase in the number of osteoblasts lining thin bone trabeculae. Group D showed a generative power concerning bone. At 90 days, there was increased bone ingrowth, and the new bone matured in all the treated implant groups. At 180 days, dense mature bone apposition was in direct contact with delayed-loaded implant surfaces. Conclusion: A radiographic examination revealed that surface modification significantly impacted osseointegration, with a strong bond between the implant surface and the surrounding bone. The histological sections at the 14-day interval revealed obvious bone remodeling activity, especially in sandblasting plus acid etching and sandblasting-modified implant surface groups. At the 90-day interval, bone ingrowth had increased, and the new bone became mature, especially in sandblasting and propolis surface modification groups. After 180 days of the delayed-loaded implant osseointegration, differences were observed between different implant-treated groups with a remarkable remodeling of the bone, especially in the propolis coating group.

Effects of intrarenal pelvic infusion of tumour necrosis factor-α and interleukin 1-ß on reno-renal reflexes in anaesthetised rats.

OBJECTIVE: Reno-renal reflexes are disturbed in cardiovascular and hypertensive conditions when elevated levels of pro-inflammatory mediators/cytokines are present within the kidney. We hypothesised that exogenously administered inflammatory cytokines tumour necrosis factor alpha (TNF-α) and interleukin (IL)-1ß modulate the renal sympatho-excitatory response to chemical stimulation of renal pelvic sensory nerves. METHODS: In anaesthetised rats, intrarenal pelvic infusions of vehicle [0.9% sodium chloride (NaCl)], TNF-α (500 and 1000 ng/kg) and IL-1ß (1000 ng/kg) were maintained for 30 min before chemical activation of renal pelvic sensory receptors was performed using randomized intrarenal pelvic infusions of hypertonic NaCl, potassium chloride (KCl), bradykinin, adenosine and capsaicin. RESULTS: The increase in renal sympathetic nerve activity (RSNA) in response to intrarenal pelvic hypertonic NaCl was enhanced during intrapelvic TNF-α (1000 ng/kg) and IL-1ß infusions by almost 800% above vehicle with minimal changes in mean arterial pressure (MAP) and heart rate (HR). Similarly, the RSNA response to intrarenal pelvic adenosine in the presence of TNF-α (500 ng/kg), but not IL-1ß, was almost 200% above vehicle but neither MAP nor HR were changed. There was a blunted sympatho-excitatory response to intrapelvic bradykinin in the presence of TNF-α (1000 ng/kg), but not IL-1ß, by almost 80% below vehicle, again without effect on either MAP or HR. CONCLUSION: The renal sympatho-excitatory response to renal pelvic chemoreceptor stimulation is modulated by exogenous TNF-α and IL-1ß. This suggests that inflammatory mediators within the kidney can play a significant role in modulating the renal afferent nerve-mediated sympatho-excitatory response.

Emerging Role of the IL-36/IL-36R Axis in Multiple Inflammatory Skin Diseases.

IL-36 is a most recent member of the IL-1 cytokine family, primarily expressed at barrier sites of the body such as the skin, lungs, and intestine. It plays a vital role in inflammation and is implicated in the development of various cutaneous; intestinal; and pulmonary disorders, including psoriasis, inflammatory bowel disease, and chronic obstructive pulmonary disease. IL-36 comprises 4 isoforms: the proinflammatory IL-36α, IL-36ß, and IL-36γ and the anti-inflammatory IL-36R antagonist. An imbalance between proinflammatory and anti-inflammatory IL-36 isoforms can contribute to the inflammatory fate of cells and tissues. IL-36 cytokines signal through an IL-36R heterodimer mediating their function through canonical signaling cacade, including the NF-B pathway. Prominent for its role in psoriasis, IL-36 has recently been associated with disease mechanisms in atopic dermatitis, hidradenitis suppurativa, neutrophilic dermatoses, autoimmune blistering disease, and Netherton syndrome. The major cutaneous source of IL-36 cytokines is keratinocytes, pointing to its role in the communication between the epidermis, innate (neutrophils, dendritic cells) immune system, and adaptive (T helper [Th]1 cells, Th17) immune system. Thus, cutaneous IL-36 signaling is crucial for the immunopathological outcome of various skin diseases. Consequently, the IL-36/IL-36R axis has recently been recognized as a promising drug target for the treatment of inflammatory disorders beyond psoriasis. This review summarizes the current update on IL-36 cytokines in inflammatory skin diseases.

Renal nerves in blood pressure regulation.

PURPOSE: This review highlights the physiological mechanisms underlying the neural regulation of the kidney, normally to maintain cardiovascular homeostasis, and in pathophysiological states of hypertension and renal disease. It is relevant because of the demonstration that bilateral renal denervation in different hypertensive groups causes a sustained reduction in blood pressure. RECENT FINDINGS: There are patients groups in whom their hypertension is resistant to antihypertensive drugs or with renal diseases in which they are contraindicated. Recently, medical devices have been developed to manipulate the sympathetic nervous system, for example, implantation of carotid sinus nerve stimulating electrodes and ablation of the renal innervation. These approaches have been relatively successful but there remains a lack of understanding of the neural mechanisms impinging on the kidney that regulate long-term control of blood pressure. SUMMARY: The observation that bilateral renal nerve ablation can reduce blood pressure represents an important therapeutic milestone. Nonetheless, questions arise as to the underlying mechanisms, the long-term consequences, whether there may be re-innervation over a number of years, or whether some unknown consequence to the denervation may arise. This may point to the development of novel compounds targeted to the innervation of the kidney.

The effects of tempol on renal function and hemodynamics in cyclosporine-induced renal insufficiency rats.

This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p < 0.05), respectively. Tempol treatment in TCs or TLCs prevented the increase in blood pressure and improved creatinine clearance and sodium excretion compared to untreated Cs. The renal vasoconstriction in Cs or LCs to NA, PE and Ang II were lower than control by ∼35-48% (all p < 0.05). In TCs or TLCs, there was enhanced renal vasoconstriction to all agonist by ∼39-114% compared to Cs. SOD is important to counterbalance the hypertensive effect of a defective NO system and to allow the normal vasoconstrictor response of the renal vasculature to adrenergic agonists and Ang II in a model of CsA-induced renal insufficiency.