Inguinal Ring RNA Sequencing Reveals Downregulation of Muscular Genes Related to Scrotal Hernia in Pigs.

Scrotal hernias (SH) are common congenital defects in commercial pigs, characterized by the presence of abdominal contents in the scrotal sac, leading to considerable production and animal welfare losses. Since the etiology of SH remains obscure, we aimed to identify the biological and genetic mechanisms involved in its occurrence through the whole transcriptome analysis of SH affected and unaffected pigs' inguinal rings. From the 22,452 genes annotated in the pig reference genome, 13,498 were expressed in the inguinal canal tissue. Of those, 703 genes were differentially expressed (DE, FDR < 0.05) between the two groups analyzed being, respectively, 209 genes upregulated and 494 downregulated in the SH-affected group. Thirty-seven significantly overrepresented GO terms related to SH were enriched, and the most relevant biological processes were muscular system, cell differentiation, sarcome reorganization, and myofibril assembly. The calcium signaling, hypertrophic cardiomyopathy, dilated cardiomyopathy, and cardiac muscle contraction were the major pathways possibly involved in the occurrence of the scrotal hernias. The expression profile of the DE genes was associated with the reduction of smooth muscle differentiation, followed by low calcium content in the cell, which could lead to a decreased apoptosis ratio and diminished muscle contraction of the inguinal canal region. We have demonstrated that genes involved with musculature are closely linked to the physiological imbalance predisposing to scrotal hernia. According to our study, the genes MYBPC1, BOK, SLC25A4, SLC8A3, DES, TPM2, MAP1CL3C, and FGF1 were considered strong candidates for future evaluation.

Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling.

Cold and other environmental factors induce "browning" of white fat depots-development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H+ leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H+ leak (IH). All inguinal beige adipocytes had robust UCP1-dependent IH comparable to brown fat, but it was about three times less sensitive to purine nucleotide inhibition. Strikingly, only âˆ¼15% of epididymal beige adipocytes had IH, while in the rest UCP1-dependent IH was undetectable. Despite the absence of UCP1 in the majority of epididymal beige adipocytes, these cells employ prominent creatine cycling as a UCP1-independent thermogenic mechanism.

Interplay between Obesity-Induced Inflammation and cGMP Signaling in White Adipose Tissue.

Current worldwide figures suggest that obesity is pandemic. Understanding the underlying molecular mechanisms would help develop viable anti-obesity therapies. Here, we assess the influence of obesity-induced inflammation on white adipocyte cyclic guanosine monophosphate (cGMP) signaling, which is beneficial for adipocyte differentiation and thermogenesis. We find that murine gonadal and not inguinal fat is prone to obesity-induced inflammation. Correspondingly, the cGMP cascade is dysregulated in gonadal but not in inguinal fat of obese mice. Analysis of two independent human cohorts reveals a defective cGMP pathway only in visceral fat of obese subjects. Congruently, cGMP signaling is dysregulated in tumor necrosis factor α (TNF-α)-treated primary white adipocytes. TNF-α-mediated suppression of sGCß1 is mediated via NF-κB, whereas PKG is repressed by JNK signaling. Additionally, TNF-α-activated JNK signaling suppresses PPARγ and aP2. Taken together, the intensity of obesity-induced inflammation dictates the amplitude of cGMP signaling dysregulation in white adipocytes through distinct pathways.

Left-sided cryptorchidism in mice with Wilms' tumour 1 gene deletion in gubernaculum testis.

A significant number of patients with germline mutations in the Wilms' tumour 1 (WT1) gene, a transcriptional factor essential for early renal and gonadal development, display cryptorchidism or non-scrotal testis position. We show here that WT1 is expressed during development in the mouse gubernacular ligament connecting the testis to the abdominal wall. Conditional inactivation of Wt1 in the gubernaculum (GU-WT1KO animals) resulted in abnormal differentiation of the gubernacula during development and, in about 40% of adult males, unilateral, always left-sided, cryptorchidism. At birth the right testis was positioned above the processus vaginalis and eventually moved into the developing scrotal pouch. In affected mutants the left testis was displaced from the normal position and the left processus vaginalis failed to form. The analysis of testicular descent at different stages of postnatal development suggests that unilateral cryptorchidism might be caused by asymmetry in the positions of the abdominal organs providing a higher degree of mobility for the left testis. Spermatogenesis in GU-WT1KO animals was blocked in cryptorchid testes located in a high pararenal position, but was maintained in testes located in a low abdominal position. Conditional inactivation of both Wt1 and androgen receptor (Ar) genes in the gubernaculum led to a bilateral asymmetrical cryptorchidism in all mutant males, with the left testis again located higher than the right one. The malformations induced by WT1 and AR deficiency in the gubernaculum and processus vaginalis, in combination with mechanical constraints on testis descent, determine the final position of the testes. In summary, our data indicate that WT1 is directly involved in gubernaculum differentiation. Taken together, the results of the study underline the complex nature of testicular descent, with an involvement in this process of several genetic factors and developmental events.

Comparison of tissue oxygen saturation in ovariohysterectomized dogs recovering on room air versus nasal oxygen insufflation.

OBJECTIVE: To compare tissue oxygen saturation in ovariohysterectomized dogs recovering postoperatively on room air versus nasal oxygen insufflation. DESIGN: Prospective clinical study. SETTING: University teaching hospital. ANIMALS: Twenty dogs undergoing ovariohysterectomy. INTERVENTIONS: Dogs were randomized to breathe either room air or 100 mL/kg/min of nasal oxygen insufflation for 2 hours postoperatively. Tissue oxygen saturation (StO(2)) was evaluated at 2 mm and 20 mm lateral to the surgical incision, as well as in the inguinal region using a noninvasive tissue oximeter. MEASUREMENTS AND MAIN RESULTS: In dogs recovered on nasal oxygen insufflation (n = 10), tissue oxygen saturation was significantly higher--20 mm from the surgical site (88.44 ± 2.50%, P = 0.02) and in the inguinal region (83.56 ± 1.91%, P = 0.032)-- compared to dogs recovered on room air (n = 10, 79.11% ± 2.50 and 77.12% ± 1.91, respectively). CONCLUSIONS: In ovariohysterectomized dogs, oxygen supplementation for 2 hours postoperatively improves tissue oxygen saturation 20 mm adjacent to the linea alba and in the inguinal region. Oxygen supplementation in postoperative dogs is an inexpensive and easily applicable method to improve tissue oxygen saturation.

Simulation and study of the behaviour of the transversalis fascia in protecting against the genesis of inguinal hernias.

Simulating the muscular system has many applications in biomechanics, biomedicine and the study of movement in general. We are interested in studying the genesis of a very common pathology: human inguinal hernia. We study the effects that some biomechanical parameters have on the dynamic simulation of the region, and their involvement in the genesis of inguinal hernias. We use the finite element method (FEM) and current models for the muscular contraction to determine the deformed fascia transversalis for the estimation of the maximum strain. We analysed the effect of muscular tissue density, Young's modulus, Poisson's coefficient and calcium concentration in the genesis of human inguinal hernia. The results are the estimated maximum strain in our simulations, has a close correlation with experimental data and the accepted commonly models by the medical community. Our model is the first study of the effect of various biological parameters with repercussions on the genesis of the inguinal hernias.

Effects of reverse Trendelenburg position and inguinal compression on femoral vein cross-sectional area in infants and young children.

This study evaluated the effects of the reverse Trendelenburg position and additional inguinal compression on the cross-sectional area of the femoral vein in paediatric patients. Seventy subjects were allocated to two groups: the infants group and the children group. Cross-sectional area of the femoral vein was measured just below the inguinal ligament using ultrasound. Three measurements were obtained for each patient: (i) supine, (ii) reverse Trendelenburg position and (iii) reverse Trendelenburg position with inguinal compression. In the infants group, femoral vein cross-sectional area increased by a mean (SD) of 21.1 (15.2) % in the reverse Trendelenburg position and by 60.7 (30.8) % in the reverse Trendelenburg position with inguinal compression; whereas in the children group, femoral vein cross-sectional area increased by 24.7 (15.8) % in the reverse Trendelenburg position and by 100.3 (50.7) % in the reverse Trendelenburg position with inguinal compression. Inguinal compression in the reverse Trendelenburg position offers a useful means of increasing femoral vein cross-sectional area in paediatric patients.

Anthropometric characteristics of the pubic arch and proper function of the defense mechanisms against hernia formation.

In 33 inguinal regions, we determined the anthropometric characteristics of the pubic arch and the anatomic structures of the suprainguinal space and assessed whether there is a relationship between anatomic features and function of the defense mechanisms. There was a low position of the pubic arch (pubic tubercle and interspinal line distance >75 mm) in 23 cases. The low-pubic-arch group showed a significantly longer inguinal ligament and a greater angle made by the superior border of the suprainguinal space and the inguinal ligament at its medial insertion. The position of the pubic arch correlated significantly with the diameter of the internal ring, the length of the inguinal ligament, and the angle made by the superior border of the suprainguinal space and the medial insertion of the inguinal ligament. A low pubic arch would represent an unfavorable condition for an adequate function of the anatomic defense mechanism against hernia.

Inguinal hernia: measurement of the biomechanics of the lower abdominal wall and the inguinal canal.

BACKGROUND: The stability of the lower abdominal wall may play a considerable role in the development of inguinal hernia. Therefore, the strength of the individual wall layers needs to be quantified. Despite numerous advances in hernia repair, comparatively few systematic biomechanic and morphometric analyses have been performed. Our aim was to establish and apply a standardised procedure for testing the abdominal wall layers' stability. METHODS: After dissecting the abdominal walls of 16 cadavers into separate layers, we used a spherical punch and a force transducer to investigate the forces necessary to foraminate the layer. In addition, maximum tensile-strength and suction tests and histologic morphometry were performed. RESULTS: The transversalis fascia was torn up on an average of 10.5 N, the peritoneum including pre- and subperitoneal tissue on 46.6 N, the aponeurosis of obliquus internus abdominis muscle on 51.7 N, and the aponeurosis of obliquus externus abdominis muscle on 92.6 N. Tensile tests of tissue strips obtained from defined areas showed comparable results. In contrast, surgical mesh revealed values between 60 and 150 N in punching tests. Left-right comparisons, as well as comparisons of the individual areas, revealed considerable intra- and inter-individual differences. CONCLUSIONS: Biological hernia repair should focus on a reinforcement of the tissue layers with the highest biomechanic stability. Reinforcement of the transversal fascia must be questioned according to our results of poor mechanical resistance.

Surgical physiology of inguinal hernia repair--a study of 200 cases.

BACKGROUND: Current inguinal hernia operations are generally based on anatomical considerations. Failures of such operations are due to lack of consideration of physiological aspects. Many patients with inguinal hernia are cured as a result of current techniques of operation, though factors that are said to prevent hernia formation are not restored. Therefore, the surgical physiology of inguinal canal needs to be reconsidered. METHODS: A retrospective study is describer of 200 patients operated on for inguinal hernia under local anaesthesia by the author's technique of inguinal hernia repair. RESULTS: The posterior wall of the inguinal canal was weak and without dynamic movement in all patients. Strong aponeurotic extensions were absent in the posterior wall. The muscle arch movement was lost or diminished in all patients. The movement of the muscle arch improved after it was sutured to the upper border of a strip of the external oblique aponeurosis (EOA). The newly formed posterior wall was kept physiologically dynamic by the additional muscle strength provided by external oblique muscle to the weakened muscles of the muscle arch. CONCLUSIONS: A physiologically dynamic and strong posterior inguinal wall, and the shielding and compression action of the muscles and aponeuroses around the inguinal canal are important factors that prevent hernia formation or hernia recurrence after repair. In addition, the squeezing and plugging action of the cremasteric muscle and binding effect of the strong cremasteric fascia, also play an important role in the prevention of hernia.

Temperature measurement in intensive care patients: comparison of urinary bladder, oesophageal, rectal, axillary, and inguinal methods versus pulmonary artery core method.

OBJECTIVE: Comparisons of urinary bladder, oesophageal, rectal, axillary, and inguinal temperatures versus pulmonary artery temperature. DESIGN: Prospective cohort study. SETTING: Intensive Care Unit of a University-Hospital. PATIENTS: Forty-two intensive care patients requiring a pulmonary artery catheter (PAC). INTERVENTION: Patients requiring PAC and without oesophageal, urinary bladder, and/or rectal disease or recent surgery were included in the study. Temperature was simultaneously monitored with PAC, urinary, oesophageal, and rectal electronic thermometers and with axillary and inguinal gallium-in-glass thermometers. Comparisons used a Bland and Altman method. MEASUREMENTS AND MAIN RESULTS: The pulmonary arterial temperature ranged from 33.7 degrees C to 40.2 degrees C. Urinary bladder temperature was assessed in the last 22 patients. A total of 529 temperature measurement comparisons were carried out (252 comparisons of esophageal, rectal, inguinal, axillary, and pulmonary artery temperature measurements in the first 20 patients, and 277 comparisons with overall methods in the last patients). Nine to 18 temperature measurement comparisons were carried out per patient (median = 13). The mean differences between pulmonary artery temperatures and those of the different methods studied were: oesophageal (0.11+/-0.30 degrees C), rectal (-0.07+/-0.40 degrees C), axillary (0.27+/-0.45 degrees C), inguinal (0.17+/-0.48 degrees C), urinary bladder (-0.21+/-0.20 degrees C). CONCLUSION: In critically ill patients, urinary bladder and oesophageal electronic thermometers are more reliable than the electronic rectal thermometer which is better than inguinal and axillary gallium-in-glass thermometers to measure core temperature.

Three-dimensional geometrical models of the inguinal region. Towards a new stereology.

In this work we studied the inguinal-abdominal region and the inguinal canal using three-dimensional geometrical models. We built the models through computer aided geometric modeling techniques on the basis of observations during real dissections, operations and diagnostic medical imaging. The obtained models show in a complete modular synthesis and with a schematic iconology the structural organization of the anatomical districts in a logic sequence of layers and topographic and spatial relationships among its components. The models represent an amazing support to anatomy and clinical anatomy for teaching and research purposes on organogenesis, surgery and diagnosis.

Gabapentin leads to remission of somatoform pain disorder with major depression.

Gabapentin, a novel antiepileptic drug, is effective in the treatment of partial seizures with and without secondary generalization. Evidence suggests that it may have mood-stabilizing and possibly antidepressant properties in bipolar depression. We report on a 48-year-old woman who had recurrent major depressive disorder. Following inguinal herniorrhaphy, she developed severe stabbing pain in the lower abdomen and inguinal area that progressed to constant pain in her whole body. She was depressive, hopeless, and had given up her social activities. A diagnosis of major depressive disorder and somatoform pain disorder was made. Antidepressants and carbamazepine were ineffective, and she had attempted suicide. Gabapentin resulted in remission of both the pain and the depressive mood at a dose of 1.800 mg/day.

[Original procedure of functional plasty of primary inguinal hernias]. / Procédé original de plastie "fonctionnelle" des hernies inguinales primaires.

We describe a novel autoplasty method we developed for primary inguinal hernia repair and report our results in nearly 150 operations. The method is based on novel principles: priority given to an individual stato-dynamic conception of the inguinal region; effect on physiological defense mechanisms of the inguinal canal; absence of tension on the sutures by autoplastic repair.

[An anatomicophysiological validation of hernioplasty in inguinal hernias]. / Vurkhu anatomo-fiziologichnata obosnovka na khernioplastikite pri ingvinalnite khernii.

Contemporary understanding of the pathogenesis of inguinal hernias modifies the approach to solution of the problem from elementary anatomical to anatomical and functional. This in turn implies a number of specific demands on their treatment, such as: 1) preserving the oblique course of the canal in the abdominal wall, 2) endeavours to utilize the functionally synergetic elements of the respective layer for plastic repair of the defect, and 3) attempt at noninterference with the pump-valve function of the canal during plastic modelling of either of the openings. In both types of inguinal hernia, posterior plasties are pathogenetically justified. Positive experience had with 37 patients, operated for inguinal hernia after the methods of Shouldice, McVay and Kukudzhanov, or by combining single elements of the latter, is shared. The series analyzed comprises 18 cases presenting indirect hernia, 8-direct, 8-simultaneously direct and indirect, and 3-recurrent hernia. The extrafascial access to Cooper's ligament described contributes to the beneficial outcome.

Lymph flow in human leg.

A little bit of RISA (0.01--0.02 ML) was injected into a lymphatic at the back of a human foot in supine and/or sitting position, and the radioactivity curves were obtained at the inguinal and/or at the middle of the thigh. Radioactivity curves at the inguinal region showed stepwise rise with the frequency of about 1/min. in subjects without edema and steep rise without staircase in patients with cardiac edema. Radioactivity curves at the middle of the thigh showed many spiky waves with the frequency of about 1/min. in supine subjects without edema, which were increased in frequency, duration and/or height in sitting subjects without edema and also in supine and sitting patients with cardiac edema. Therefore, it may be said that there are rhythmic lymph flows in lower leg of subjects without edema and of patients with cardiac edema not only in supine but also in sitting position, and also that lymphatic contractility plays some role in propelling lymph in human leg.

The strength of tissue against individual sutures in structures involved in the repair of inguinal hernia.

The strength of tissue against individual sutures in structures used in the repair of inguinal hernia was tested in situ in 19 cadavers. Altogether 465 measurements were made. Three different layers were investigated, and the mean tissue strength to a single suture was recorded as the mean of all means for each preparation and aspect as follows. (1) The superficial layer (external oblique aponeurosis). Superior aspect 5.3 kp, inferior aspect 5.5 kp. (2) Middle layer. Superior aspect (internal abdominal oblique), 5.9 kp; inferior aspect (inferior border of the inguinal ligament), 6.8 kp. (3) Deep layer. Superior aspect (transversalis fascia), 5.3 kp; inferior aspect (ilio-pubic tract), 6.9 kp. In Cooper's ligament the mean holding power of the tissue against a single suture was found to be 9.1 kp. The site of the most medial of the sutures in the superior aspect of the middle layer corresponds to the conjoined tendon, and the mean tissue strength to this suture was 11.0 kp. The findings thus suggest that the strengths of the tissues of the anterior and posterior walls of the inguinal canal are roughly equal. The structures making up the conjoined tendon and Cooper's ligament were strongest, however, and showed tissue strengths nearly twice those of other structures.