Machine learning-based assessment and simulation of land use modification effects on seasonal and annual land surface temperature variations.

Rapid urban sprawl adversely impacts the local climate and the ecosystem components. Islamabad, one of South Asia's green and environment-friendly capitals, has experienced major Land Use Land Cover (LULC) changes over the past three decades consequently, elevating the seasonal and annual Land Surface Temperature (LST) in planned and unplanned urban areas. The focus of this study was to quantify the fluctuations in LULC and LST in planned and unplanned urban areas using Landsat data and Machine Learning algorithms involving the Support Vector Machine (SVM) over the 1990-2020 data period. Moreover, hybrid Cellular Automata-Markov (CA-Markov) and Artificial Neural Network (ANN) models were employed to project the future changes in LULC and annual LST, respectively, for the years 2035 and 2050. The findings of the study reveal a distinct difference in seasonal and annual LST in planned and unplanned areas. Results showed an increase of ∼22 % in the built-up area but vegetation and bare soil decreased by ∼10 % and ∼12 %, respectively. Built-up land showed a maximum annual mean LST followed by bare-soil and vegetative surfaces. Seasonal analysis showed that summer months experience the highest LST, followed by spring, autumn and winter. Future projections revealed that the built-up areas (∼27 % in 2020) are likely to increase to ∼37 % and ∼50 %, and the areas under the highest annual mean LST class i.e., ≥28 °C are likely to increase to ∼19 % and ∼21 % in planned, and ∼38 % and ∼42 % in unplanned urban areas for the years 2035 and 2050, respectively. Planned areas have better temperature control with urban green spaces, and controlled infrastructure. The Capital Development Authority of Islamabad may be advised to control the expansion of built-up areas, grow urban forests, and thus mitigate the possible Urban Heat Island (UHI) effect.

Patterns of Common Dermatological Conditions among Children and Adolescents in Pakistan.

Background and Objectives: Dermatological disorders are highly prevalent among children in Pakistan. The present cross-sectional study aims to identify the spectrum of dermatological conditions among children and adolescents in Pakistan. Materials and Methods: A total of 582 patients (50.9% males; 49.1% females) were included in the study based on their age (5.7 ± 4.1 years), dermatological condition, and epidemiology. The youngest patient was aged ten days, whereas the eldest was seventeen. Age criteria were further stratified into three categories: infants and toddlers (≤5 years), children (≥5 to <12 years), and adolescents (≥12 to <18 years). Amongst them, the majority was from Punjab (81.6%), while the other regions included were Azad Jammu and Kashmir (14.4%), Islamabad (3.3%), and Khyber Pakhtunkhwa (0.7%). Results: Scabies was the highest reported skin condition with 281 (45.55%) patients, followed by 114 (19.6%) with eczema, 60 (10.3%) with dermatitis, 33 (5.7%) with tinea capitis, 17 (2.9%) with tinea corporis, 16 (2.7%) with impetigo, and 15 (2.6%) with folliculitis. Other conditions include urticaria, burns, infections, pediculosis, tinea inguinalis, tinea faciei, nappy rashes, alopecia, warts, tinea incognito, tinea cruris, and acne vulgaris. The chi-squared test showed a high prevalence of tinea corporis and acne among adolescents (12-17 years), whereas eczema, dermatitis, and impetigo were more prevalent among infants and toddlers. Conclusions: Pets or livestock and poor hygiene were found to be highly reported risk factors for many dermatological conditions like scabies and fungal infections. Dermatological conditions are common in younger individuals, but unfortunately, many children do not receive the desired medical assistance.

Analysis of the relationship among land surface temperature (LST), land use land cover (LULC), and normalized difference vegetation index (NDVI) with topographic elements in the lower Himalayan region.

Land Surface Temperature (LST) affects exchange of energy between earth surface and atmosphere which is important for studying environmental changes. However, research on the relationship between LST, Land Use Land Cover (LULC), and Normalized Difference Vegetation Index (NDVI) with topographic elements in the lower Himalayan region has not been done. Therefore, the present study explored the relationship between LST and NDVI, and LULC types with topographic elements in the lower Himalayan region of Pakistan. The study area was divided into North-South, West-East, North-West to South-East and North-East to South-East directions using ArcMap 3D analysis. The current study used Landsat 8 (OLI/TIRS) data from May 2021 for LULC and LST analysis in the study area. The LST data was obtained from the thermal band of Landsat 8 (TIRS), while the LULC of the study areas was classified using the Maximum Likelihood Classification (MLC) method utilizing Landsat 8 (OLI) data. TIRS collects data for two narrow spectral bands (B10 and B11) with spectral wavelength of 10.6 µm-12.51 µm in the thermal region formerly covered by one wide spectral band (B6) on Landsat 4-7. With 12-bit data products, TIRS data is available in radiometric, geometric, and terrain-corrected file format. The effect of elevation on LST was assessed using LST and elevation data obtained from the USGS website. The LST across LULC types with sunny and shady slopes was analyzed to assess the influence of slope directions. The relationship of LST with elevation and NDVI was examined using correlation analysis. The results indicated that LST decreased from North-South and South-East, while increasing from North-East and South-West directions. The correlation coefficient between LST and elevation was negative, with an R-value of -0.51. The NDVI findings with elevation showed that NDVI increases with an increase in elevation. Zonal analysis of LST for different LULC types showed that built-up and bare soil had the highest mean LST, which was 35.76 °C and 28.08 °C, respectively, followed by agriculture, vegetation, and water bodies. The mean LST difference between sunny and shady slopes was 1.02 °C. The correlation between NDVI and LST was negative for all LULC types except the water body. This study findings can be used to ensure sustainable urban development and minimize urban heat island effects by providing effective guidelines for urban planners, policymakers, and respective authorities in the Lower Himalayan region. The current thermal remote sensing findings can be used to model energy fluxes and surface processes in the study area.

Evaluation of Potentially Toxic Trace Metals and Associated Health Risk Assessment in Buffalo Milk.

The contamination of toxic trace metals in the food chain is one of the major threats to human health. Milk is part of a balanced diet, which is essential for proper growth, but the ingestion of contaminated milk may cause chronic health disorders. The present study is focused on the assessment of contamination of toxic trace metals in buffalo milk and the associated health risks to the consumers of Abbottabad, Pakistan. Standard analytical methods were employed to quantify the metal contents in the milk samples collected from various shops and homes in the months from June 2021 to October 2021. Health risk assessment was accomplished by computing estimated daily intake (EDI), health risk index (HRI), target hazard quotient (THQ), hazard index (HI), and target cancer risk (TCR). On a comparative basis, the mean concentration of Cr was found to be highest in both shop and home milk samples (101.3 ± 45.33 and 54.11 ± 24.20 mg/L, respectively), followed by Pb, Zn, Ni, and Cd levels. In buffalo milk collected from homes, the highest concentration of the metals was found in October, followed by July, September, June, and August. In shop milk, the increasing trend of metal contents was July > October > September > June > August. Significantly strong positive relationships were noted between the metal concentrations in the milk samples. Multivariate cluster analysis and principal component analysis exhibited significant anthropogenic contributions of the metals in buffalo milk. Mostly, the EDI and HRI values were exceeding the recommended limits; however, THQ, HI, and TCR showed that the intake of these metals through milk consumption was within the safe limit and thus revealed no significant carcinogenic or non-carcinogenic risks to the consumers. It is high time to ensure the continuous monitoring of organic/inorganic toxins in the milk and concerned authorities should take strict measures to control the contamination of milk and other food products.

Inter-Relationship Between a Transcriptional Regulator of Flagella Genes cj0440c and Thiamine Metabolic Pathway in Campylobacter jejuni.

Campylobacter jejuni is a major cause of gastroenteritis in humans. It has been reported that the pathogenesis of C. jejuni is closely related to the formation, adhesion, and invasion of flagella toxin in host epithelial cells. A putative transcriptional regulator, known as cj0440c, is thought to be involved in the regulation of flagellar synthesis. However, confirmation of this hypothesis requires deep insight into the regulation mechanism of cj0440c and its possible relationship with different antibiotics. Therefore, the study explained here was designed to determine the relationship and function (phenotypically and genotypically) of cj0440c in the flagellar synthesis of C. jejuni NCTC11168. The study determined the mode of expression of cj0440c and flagella-related genes under exposure to various drugs. To verify the involvement of cj0440c protein in the metabolic pathway of thiamine, an enzymatic hydrolysis experiment was performed and analyzed through the application of mass spectrometry. The overexpression vector of C. jejuni NCTC11168 was also constructed to find out whether or not target genes were regulated by cj0440c. The findings of the study showed that cj0440c and other flagella-related genes were expressed differentially under the influence of various antibiotics including erythromycin, tylosin, azithromycin, gentamicin, etimicin, enrofloxacin, gatifloxacin, tetracycline, and tigecycline. The analysis showed that the cj0440c protein did not catalyze the degradation of thiamine. In conclusion, the study aids in the understanding of the inter-relationship between the regulatory mechanism of flagella genes and the thiamine metabolic pathway.

Trends and projections of land use land cover and land surface temperature using an integrated weighted evidence-cellular automata (WE-CA) model.

Land use land cover (LULC) change has become a major concern for biodiversity, ecosystem alteration, and modifying the climatic pattern especially land surface temperature (LST). The present study assessed past and predicted future LULC and LST change in the Swabi District of Pakistan. LULC maps were generated from satellite data for years 1987, 2002, and 2017 using supervised classification. Mean LST and its areal change were estimated for different LULC classes from thermal bands of satellite images. LULC and LST were projected for the year 2047 using the integrated weighted evidence-cellular automata (WE-CA) model and a regression equation developed in this study, respectively. LULC change revealed an increase of > 5% in the built-up while a decrease in the agricultural area by ~ 9%. There was an increase of ~ 63% area in the LST class ≥ 27 °C which may create urban heat island (UHI). Simulation results indicated that the built-up area will further be increased by ~ 3% until 2047. Area associated with LST class > 30 °C indicated a further increase of ~ 38% till 2047 with reference to year 2017. Findings of this study suggested proper utilization of LULC in order to mitigate the creation of UHIs associated with urbanization and built-up areas.

Peripheral and Spinal Mechanisms Involved in Electro-Acupuncture Therapy for Visceral Hypersensitivity.

One of the important characteristic features of clinically significant gastrointestinal disorders is visceral hypersensitivity (VH). Pain sensitization or VH is a big challenge for clinicians and becomes a very thorny work in clinical practices; the therapeutic efficacy for VH results in limited success. A popular second therapy that is being approved for the induction of analgesia and attenuates VH with fewer side effects includes electro-acupuncture (EA). Different peripheral and spinal neurological chemicals, including neurotransmitters, neuropeptides, and cytokines, and different signaling pathways were associated with EA treatment in VH. Despite the higher acceptance of EA, the underlying mechanism still needs to be further explored. In this paper, we review the available literature to find the peripheral and spinal mechanisms involved in EA to relieve VH.

The influence of type of visual image and gender on the perception of horizontality: a subjective visual horizontal (SVH) study.

BACKGROUND: The graviceptive otolith function can be measured using subjective visual horizontal (SVH) testing. Nevertheless, more research efforts are required to understand the essential variables affecting SVH. OBJECTIVE: The aim of the present study was to determine the effects of type of visual image and gender on subjective visual horizontal (SVH) perception among healthy adults. MATERIALS AND METHODS: In this comparative study, 50 healthy young adults were enrolled. While in an upright body position, they were required to report their perception of horizontality for two types of visual images (solid line and arrow pattern) using a computerized SVH device. RESULTS: The arrow pattern produced significantly bigger SVH angles than the solid line (p < .001). In contrast, no significant influence of gender was found on SVH results (p = .743), Based on the statistical outcomes, the preliminary normative data for SVH were established. CONCLUSIONS AND SIGNIFICANCE: The arrow pattern (a more complex visual image) produced bigger SVH deviations than the simple solid line image. In contrast, the horizontality perception does not appear to be affected by gender. The preliminary normative SVH data gathered from the present study can be beneficial for clinical and future research applications.

A Systematic Review on Cloud Storage Mechanisms Concerning e-Healthcare Systems.

As the expenses of medical care administrations rise and medical services experts are becoming rare, it is up to medical services organizations and institutes to consider the implementation of medical Health Information Technology (HIT) innovation frameworks. HIT permits health associations to smooth out their considerable cycles and offer types of assistance in a more productive and financially savvy way. With the rise of Cloud Storage Computing (CSC), an enormous number of associations and undertakings have moved their healthcare data sources to distributed storage. As the information can be mentioned whenever universally, the accessibility of information becomes an urgent need. Nonetheless, outages in cloud storage essentially influence the accessibility level. Like the other basic variables of cloud storage (e.g., reliability quality, performance, security, and protection), availability also directly impacts the data in cloud storage for e-Healthcare systems. In this paper, we systematically review cloud storage mechanisms concerning the healthcare environment. Additionally, in this paper, the state-of-the-art cloud storage mechanisms are critically reviewed for e-Healthcare systems based on their characteristics. In short, this paper summarizes existing literature based on cloud storage and its impact on healthcare, and it likewise helps researchers, medical specialists, and organizations with a solid foundation for future studies in the healthcare environment.

Electroacupuncture intervention of visceral hypersensitivity is involved in PAR-2-activation and CGRP-release in the spinal cord.

Electroacupuncture (EA) relieves visceral hypersensitivity (VH) with underlying inflammatory bowel diseases. However, the mechanism by which EA treats ileitis-induced VH is not clearly known. To assess the effects of EA on ileitis-induced VH and confirm whether EA attenuates VH through spinal PAR-2 activation and CGRP release, goats received an injection of 2,4,6-trinitro-benzenesulfonic-acid (TNBS) solution into the ileal wall. TNBS-injected goats were allocated into VH, Sham acupuncture (Sham-A) and EA groups, while goats treated with saline instead of TNBS solution were used as the control. Goats in EA group received EA at bilateral Hou-San-Li acupoints for 0.5 h at 7 days and thereafter repeated every 3 days for 6 times. Goats in the Sham-A group were inserted with needles for 0.5 h at the aforementioned acupoints without any hand manipulation and electric stimulation. Visceromotor responses to colorectal distension, an indicator of VH, were recorded by electromyography. The terminal ileum and thoracic spinal cord (T11) were sampled for evaluating ileitis at days 7 and 22, and distribution and expression-levels of PAR-2, CGRP and c-Fos on day 22. TNBS-treated-goats exhibited apparent transmural-ileitis on day 7, microscopically low-grade ileitis on day 22 and VH at days 7-22. Goats of Sham-A, VH or EA group showed higher (P < 0.01) VH at days 7-22 than the Control-goats. EA-treated goats exhibited lower (P < 0.01) VH as compared with Sham-A or VH group. Immunoreactive-cells and expression-levels of spinal PAR-2, CGRP and c-Fos in the EA group were greater (P < 0.01) than those in the Control group, but less (P < 0.01) than those in Sham-A and VH groups on day 22. Downregulation of spinal PAR-2 and CGRP levels by EA attenuates the ileitis and resultant VH.

Disposition of cyadox in domesticated cats following oral, intramuscular, and intravenous administration.

Cyadox (CYX) is a synthetic antibacterial agent of quinoxaline with much lower toxic effects. A safety criterion of CYX for clinical use was established by studying the pharmacokinetics and metabolism of CYX after oral (PO), intramuscular (IM), and intravenous (IV) administration. CYX was administered in six domesticated cats (three males and three females) by PO (40 mg/kg.b.w.), IM (10 mg/kg.b.w.), and IV (10 mg/kg.b.w.) routes in a crossover pattern. Highly sensitive liquid chromatography with ultraviolet detection (HPLC-UV) method was developed for detection of CYX and its metabolites present in plasma, urine, and feces. The bioavailability of CYX after PO and IM routes was 4.37% and 84.4%. The area under curves (AUC), mean resident time (MRT), and clearance (CL) of CYX and its metabolites revealed that CYX quickly metabolized into its metabolites. The total recovery of CYX and its main metabolites was >60% after each route. PO delivery suggesting first pass effect in cats that might make this route suitable for intestinal infection and IM injection could be better choice for systemic infections. Less ability of glucuronidation did not show any impact on CYX metabolism. The findings of present study provide detailed information for evaluation of CYX.

Modification of the Superomedial Pedicle in Wise-Pattern Breast Reduction: New Sling Suspension Technique to Prevent (Pseudo) Ptosis.

BACKGROUND: The combination of the superomedial pedicle with the traditional Wise-pattern skin resection has gained increasing popularity for its versatility and ability to achieve significant reduction of breast parenchyma and skin envelope. METHODS: The author describes a reproducible new dermal suspension technique for cranial stabilization and fixation of the superomedial pedicle in Wise inverted T breast reductions to prevent pseudoptosis. RESULTS: One patient had a small dermal skin abscess caudal from the right areola as a tissue reaction on the remaining suture. The other peri- and post-operative cases were uncomplicated. Two patients experienced a two-week postoperative pain in the areas treated by liposuction. There was no reduced or increased sensibility of the nipple-areola complex. No signs of (pseudo) ptosis were seen. There was a 100% patient satisfaction rate. CONCLUSION: Our technique denoted to a direct support of the pedicle using a non-interrupted dermal suspension flap continued with the pedicle to be a medial, caudal and lateral support for the pedicle. The dermal sling reduced the anterior force generated by the pedicle. The pedicle enfolded by the dermal flap formed a vital basis for ingrowth in the surrounding tissue.

Analysis and simulation of land cover changes and their impacts on land surface temperature in a lower Himalayan region.

Rapid urbanization is changing the existing patterns of Land Use Land Cover (LULC) globally which is consequently increasing the Land Surface Temperature (LST) in many regions. Present study was focused on estimating the current and simulating the future LULC and LST trends in the alpine environment of lower Himalayan region of Pakistan. Past patterns of LULC and LST were identified through the Support Vector Machine (SVM) and multi-spectral Landsat satellite images during 1987-2017 data period. The Cellular automata (CA) model and Artificial Neural Network (ANN) were applied to simulate future (years 2032 and 2047) LULC and LST changes, respectively, using their past patterns. CA model was validated for the simulated and the estimated LULC for the year 2017 with an overall Kappa (K) value of 0.77 using validation modules in QGIS and IDRISI software. ANN method was validated by correlating the observed and simulated LST for the year 2017 with correlation coefficient (R) and Mean Square Error (MSE) values of 0.81 and 0.51, respectively. Results indicated a change in the LULC and LST for instance the built-up area was increased by 4.43% while agricultural area and bare soil were reduced by 2.74% and 4.42%, respectively, from 1987 to 2017. The analysis of LST for different LULC classes indicated that built-up area has highest temperature followed by barren, agriculture and vegetation surfaces. Simulation of future LULC and LST showed that the built-up area will be increased by 2.27% (in 2032) and 4.13% (in 2047) which led 42% (in 2032) and 60% (in 2047) of the study area as compared to 26% area (in 2017) to experience LST greater than 27 °C. A strong correlation between built-up area changes and LST was thus found signifying major challenge to urban planners mitigating the consequent of Urban Heat Island (UHI) phenomenon. It is suggested that future urban planning should focus on urban plantation to counter UHI phenomena in the region of lower Himalayas.

The influences of age, gender and geometric pattern of visual image on the verticality perception: A subjective visual vertical (SVV) study among Malaysian adults.

OBJECTIVES: Subjective visual vertical (SVV) is a simple, quick and reliable test for measuring utricular function. The literature on the effects of fundamental demographic variables such as age and gender on SVV is inconclusive and should be supported by research with larger samples. The aim of the present study was to determine the influences of age, gender and geometric pattern of visual image on SVV among healthy adults. STUDY DESIGN: This study employed a repeated measures design. SETTINGS: Otorhinolaryngology Clinic, Hospital Universiti Sains Malaysia, Malaysia. PARTICIPANTS: Eligible Malaysian adults (N = 187, aged 21-75 years) were recruited and categorised into young (N = 60), middle-aged (N = 66) and older (N = 61) groups. Most of them were Malay, and 51.3% were men. MAIN OUTCOME MEASURES: Subjective visual vertical angles (in degrees) were determined from each participant in a static upright condition using a computerised SVV device. They were asked to indicate their verticality perception for three types of visual images (solid line, dotted line and arrow pattern). RESULTS: Three-way mixed ANOVA revealed insignificant influences of age and gender on SVV results (P > 0.05). In contrast, mean SVV angles were significantly higher for the arrow pattern than for other visual images (P = 0.004). CONCLUSION: While the insignificant influences of age and gender on static SVV are further ascertained with larger samples, the perception of verticality is less accurate when aligning a more geometrically complex visual image (ie, arrow pattern). Further SVV research on vestibular-disordered patients is beneficial, particularly to verify the normative data obtained with this complex visual image.

Electroacupuncture Attenuates Visceral Hypersensitivity by Inhibiting JAK2/STAT3 Signaling Pathway in the Descending Pain Modulation System.

Electroacupuncture (EA) has been used for treating visceral hypersensitivity (VH). However, the underlying molecular mechanism remains unclear. This study was aim to testify the effect of EA on ileitis-provoked VH, and to confirm whether EA attenuates VH through Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) signaling pathway in the periaqueductal gray (PAG)-the rostral ventromedial medulla (RVM)-the spinal cord dorsal horn (SCDH) axis. Methods: Goats were anesthetized and laparotomized for injecting 2,4,6-trinitro-benzene-sulfonic acid (TNBS)-ethanol solution (30mg TNBS dissolved in 40% ethanol) into the ileal wall to induce VH. EA was treated for 30min from day 7, then every 3 days for six times. VH was assessed by visceromotor response (VMR) and pain behavior response to 20, 40, 60, 80, and 100 mmHg colorectal distension pressures at day 7, 10, 13, 16, 19, and 22. The spinal cord in the eleventh thoracic vertebra and the brain were collected at day 22. The protein and mRNA levels of IL-6, JAK2, and STAT3 in the SCDH were detected with western blot and qPCR, respectively. The distribution of these substances was observed with immunohistochemistry in the ventrolateral PAG (vlPAG), RVM (mainly the nucleus raphe magnus, NRM), SCDH, the nucleus tractus solitaries (NTS) and the dorsal motor nucleus of vagi (DMV). Results: Goats administered with TNBS-ethanol solution showed diarrhea, enhanced VMR and pain behavior response, and increased IL-6, phosphorylated JAK2 and STAT3 (pJAK2 and pSTAT3) in the vlPAG, NRM, NTS and DMV, and their protein and mRNA levels in the SCDH. EA relieved diarrhea, VMR and pain behavior response, decreased IL-6, pJAK2 and pSTAT3 levels in the vlPAG, NRM, SCDH, NTS, and DMV except for pSTAT3 in the DMV, but did not affect mRNA level of these three substances in the SCDH. Conclusion: EA attenuates VH probably through inhibiting JAK2/STAT3 signaling pathway in the PAG-RVM-SCDH axis.

Recovery of Chicken Growth Plate by Heat-Shock Protein 90 Inhibitors Epigallocatechin-3-Gallate and Apigenin in Thiram-Induced Tibial Dyschondroplasia.

Tibial dyschondroplasia (TD) is an important tibiotarsal bone disorder characterized by an avascular and nonmineralized growth plate; it is attributed to abnormal differentiation of chondrocytes and causes lameness. Heat-shock protein 90 (Hsp90) is a proangiogenic factor in animal tissues; however, its gene expression increases in cases of chicken TD. The objective of this study was to evaluate the efficacy of epigallocatechin-3-gallate (EGCG) and apigenin in thiram-induced TD birds; these substances were used because of their Hsp90 inhibitory activities. The histologic study of growth plates was carried out with hematoxylin and eosin staining, and the Hsp90 gene expression was examined by reverse transcription quantitative real-time PCR. Results showed that as compared to a control group, TD-affected birds displayed changes in chondrocyte differentiation, with lack of blood vessels, and an increased expression of Hsp90 was observed significantly (P < 0.05). However, on administering the EGCG and apigenin to TD-affected birds, the normal chondrocyte columnar organization was restored with vascularization and decreased Hsp90 expression activity (P < 0.05), which ultimately abrogated the lameness. Our results suggested that Hsp90 is the key factor in the development of TD, and EGCG and apigenin have a novel effect on Hsp90 inhibition properties, thus reducing the lameness and leg deformity in chicken broilers.

Visceral pain triggered by traction on the ileocecal ligament with ileitis.

BACKGROUND: Visceral pain is a common symptom of several gastrointestinal disorders. Despite tremendous progress in understanding its basic mechanisms, it remains a significant health challenge for clinicians. The present study quantified the intensity of visceral pain using ileocecal ligament traction on an inflamed ileum in goats. MATERIALS AND METHODS: A total of 36 male goats weighing 20.05±2.1 kg were randomly allocated equally into a 2,4,6-trinitrobenzenesulfonic acid (TNBS) group (n=18) and a saline group (n=18). Ileitis was induced via the injection of 30 mg TNBS dissolved in 30% ethanol into the ileal wall through a laparotomy. An equal volume of normal saline was injected into the ileal wall of the saline goats. Behavioral responses to traction (2, 4, and 6 N) on the ileocecal ligament were observed on days 3, 7, and 14. Six goats from each group received a laparotomy and partial intestinal resection for ileal sample collection immediately after behavioral testing on days 3, 7, and 14. Ileal histopathological changes were assessed and concentrations of myeloperoxidase, IL-1ß, IL-6, and TNFα investigated using enzyme-linked immunosorbent assay. RESULTS: The TNBS-treated goats exhibited remarkably increased macroscopic scores, mast-cell counts, myeloperoxidase, and TNFα concentrations on days 3 and 7 compared to the saline group, and increased microscopic scores and IL-1ß and IL-6 concentrations on days 3-14. The TNBS-treated goats exhibited behavioral changes in response to traction in the same pattern as their microscopic changes and cytokine levels. The traction force correlated positively with pain-behavior responses. CONCLUSION: Traction on the ileocecal ligament of goats with ileitis provoked an apparent, stable, and reproducible ileum-derived pain. The current model may be helpful in evaluating the efficacy of new drugs for the management of visceral pain and in investigating its underlying mechanisms.

A novel model for studying ileitis-induced visceral hypersensitivity in goats.

BACKGROUND: Visceral hypersensitivity (VH) is a common condition in many gastrointestinal disorders such as inflammatory bowel diseases (IBDs) in human and animals. Most studies often induce Crohn's disease/colitis to investigate VH in small experimental animals. Although farm animals commonly suffer from IBDs, their VH has not been investigated so far. Because goats can suffer from Johne's disease, a naturally occurring Crohn's-like disease, they may be suitable to be used for studying the mechanism underlying VH in common intestinal disorders of large animals. In the present study, 60 healthy goats of either sex were equally divided into a 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) group and saline group. A volume of 1.2 ml of TNBS-ethanol solution (30 mg TNBS in 40 % ethanol) or an equal volume of isotonic saline was injected into the wall of the terminal ileum through laparotomy. The severity of the developing ileitis was determined according to macro- and microscopic pathologic scores and the levels of myeloperoxidase, interleukin-1ß, interleukin-6 and tumor necrosis factor-α, and VH was evaluated with visceromotor responses (VMR) to colorectal distension on days 3, 7, 14, 21 and 28. VMRs were assessed with a continuous ramp distention mode with 6 s for each pressure (20, 40, 60, 80 and 100 mmHg). RESULTS: Compared to the saline group, the TNBS-treated goats showed apparent transmural pathological changes and a significant increase (P < 0.05) in macroscopic and microscopic change scores, and levels of myeloperoxidase, interleukin-1ß, interleukin-6 and tumor necrosis factor-α in the ileum, and VMR to colorectal distension. The goats exhibited apparent ileitis at days 3 to 21, and VH at days 7 to 28 following TNBS treatment. CONCLUSION: This experiment successfully established a reproducible ileitis and VH with administration of TNBS-ethanol solution in the ileal wall of goats. This model is useful for studying the pathogenesis of the IBD and the mechanism underlying VH, and for evaluating the efficacy of new therapeutic regimens.

Visceral Hypersensitivity Is Provoked by 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Ileitis in Rats.

BACKGROUND AND AIMS: Crohn's Disease (CD), a chronic Inflammatory Bowel Disease, can occur in any part of the gastrointestinal tract, but most frequently in the ileum. Visceral hypersensitivity contributes for development of chronic abdominal pain in this disease. Currently, the understanding of the mechanism underlying hypersensitivity of Crohn's ileitis has been hindered by a lack of specific animal model. The present study is undertaken to investigate the visceral hypersensitivity provoked by 2,4,6-trinitrobenzene sulfonic (TNBS)-induced ileitis rats. METHODS: Male Sprague-Dawley rats were anaesthetized and laparotomized for intraileal injection of TNBS (0.6 ml, 80 mg/kg body weight in 30% ethanol, n = 48), an equal volume of 30% Ethanol (n = 24), and Saline (n = 24), respectively. Visceral hypersensitivity was assessed by visceromotor responses (VMR) to 20, 40, 60, 80, and 100 mmHg colorectal distension pressure (CRD) at day 1, 3, 7, 14, 21, and 28. Immediately after CRD test, the rats were euthanized for collecting the terminal ileal segment for histopathological examinations and ELISA of myleoperoxidase and cytokines (TNF-α, IL-1ß, IL-6), and dorsal root ganglia (T11) for determination of calcitonin gene-related peptide by immunohistochemistry, respectively. RESULTS: Among all groups, TNBS-treatment showed transmural inflammation initially at 3 days, reached maximum at 7 days and persisted up to 21 days. The rats with ileitis exhibited (P < 0.05) VMR to CRD at day 7 to day 21. The calcitonin gene-related peptide-immunoreactive positive cells increased (P < 0.05) in dorsal root ganglia at day 7 to 21, which was persistently consistent with visceral hypersensitivity in TNBS-treated rats. CONCLUSION: TNBS injection into the ileum induced transmural ileitis including granuloma and visceral hypersensitivity. As this model mimics clinical manifestations of CD, it may provide a road map to probe the pathogenesis of gut inflammation and visceral hypersensitivity, as well as for establishing the therapeutic protocol for Crohn's ileitis.