Associations between child abuse and neglect, and dento-alveolar injuries in a Children's hospital population.

BACKGROUND/AIM: The purpose of this study was to identify social variables common to children with dento-alveolar trauma (DAT) and child abuse and neglect (CAN) in a large children's hospital population. METHODS: Emergency department data from an urban trauma Level 1 children's hospital were queried between December 02, 2017 and September 30, 2022 to identify children with both DAT and CAN. Patients with DAT and CAN were compared to DAT-only children in a case-control study design. Descriptive statistics were used to report characteristics of children in case and control groups. Chi-Squared and Fisher's exact tests were used to compare cases and controls. The level of significance was set at p ≤ .05. RESULTS: In total, 14 children who had DAT and CAN reported simultaneously comprised the case group. A total of 42 children with DAT-only, age/sex matched with cases, comprised the control group. Mean (SD) age of cases was 10.4 (±4) and controls was 10.1 (±3.9) years-old. Eight cases (57.1%) and 24 controls (57.1%) were female. No statistical differences (p = .05) were present for language, race, insurance coverage, parental custody, legal guardianship, and type of residence for cases versus controls. Five (35.7%) cases had a special need versus 4 (9.5%) controls and was statistically different (p = .03). Nine (64.3%) cases had behavioral problems versus 13 (31%) controls (p = .05). Cases were more likely to have facial injuries than controls (74.3 vs. 31%), however no significant differences were present for total number of injured teeth, head injury or neck injury between cases and controls. In half of cases, the perpetrator reported was the sibling. CONCLUSIONS: Demographics did not predict CAN in children with dental injuries. Sibling violence should be considered in suspected CAN children.

Risk of concomitant traumatic brain injuries in children with traumatic dental injuries in a pediatric emergency department: A case-control study.

BACKGROUND: Children with traumatic dental injuries (TDIs) may simultaneously sustain a traumatic brain injury (TBI). The aim of this study was to investigate the risk of concomitant TBI in children with TDIs. METHODS: Children (≤ 18 years) who sought treatment at the emergency department of a major children's hospital for TDIs from 2010 through 2019 were identified. Children with a concomitant TBI were assigned as case patients (TDI and TBI). Two control patients (TDI only) were randomly age- and sex-matched with each case patient. Associations between variables of TDI and concomitant TBI were tested using 6 logistic regression models. RESULTS: Of 2,126 children with TDIs, 119 had concomitant TBIs (case patients). The control group consisted of 238 children with TDIs only who were age- and sex-matched with case patients. Mean (SD) age of children was 8.9 (4.8) years. Twenty-seven percent of case patients were female vs 32% of control patients. There was a statistically significant direct association between total number of injured teeth and concomitant TBIs (P = .01; odds ratio, 2.42; 95% CI, 1.22 to 4.79). For every tooth injured, the odds of concomitant TBI increased by 45% (P < .001; odds ratio, 1.45; 95% CI, 1.18 to 1.79). Number of displaced teeth, presence of avulsion or intrusion, number of fractured teeth, presence of complicated tooth fracture, and presence of alveolar fracture were not significantly associated with the odds of concomitant TBI. CONCLUSIONS: The total number of injured teeth was positively associated with higher odds of concomitant TBI in this setting. PRACTICAL IMPLICATIONS: In an emergency department setting, children with various types of TDIs sustained concomitant TBIs. For every tooth injured, the odds of concomitant TBI increased by 45%. Clinicians must systematically evaluate children with any TDI to rule out the possibility of concomitant TBI.

Characteristics, treatment outcomes and direct costs of tooth avulsion in children treated at a major hospital.

BACKGROUND/AIMS: Avulsion of a permanent tooth is one of the most severe traumatic dental injuries, comprising an estimated 0.5%-16% of all dental injuries. The aim of this study was to estimate the direct financial costs of tooth avulsion in children based on stage of root maturity and the occurrence of ankylosis and to report patients' characteristics and outcomes of treatment. MATERIALS AND METHODS: A retrospective review of the dental records of children ages 6-18 who sustained a permanent tooth avulsion from 2010 to 2020 was completed. Relative Value Units (RVUs) were used to calculate the estimated cost of dental trauma care over the 2-year post-injury period for five different scenarios of avulsed teeth based on the stage of root maturity, the occurrence of ankylosis and whether the tooth was replanted. RESULTS: There were 452 avulsed permanent teeth in 348 patients. Of those, 157 teeth were included in the cost analysis. Overall, the average direct dental cost of avulsion was 46.4 RVUs equal to $1619 USD based on the 2021 conversion rate ($34.89 per RVU). Direct costs ranged between 40 RVUs ($1396) and 52.8 RVUs ($1842) depending on the root maturation and ankylosis status or whether the tooth was replanted; however, ANOVA test did not show any statistically significant differences between the mean RVUs of different groups (p = .85). Patients returned 9.5 times on average over the 2-year study period for dental trauma care after avulsion. CONCLUSION: The average direct cost of tooth avulsion within the limits of this study was $1619 USD. On average, patients returned for 9.5 follow-up visits after the avulsion. The stage of root maturity, the occurrence of ankylosis and whether the tooth was replanted or not were not significantly associated with the direct cost of dental care.

Traumatic dental injuries in high school athletes in the United States of America from 2005 to 2020.

BACKGROUND/AIM: Participation in sports activities is a source of dental injury. Despite recommendations for the use of mouthguards, athletes underutilize them. The aim of this study was to provide estimates of dental injuries, the mechanism of injuries and the utilization of mouthguards in high school sports. MATERIALS AND METHODS: This study was a secondary analysis of an existing dataset of a convenience sample of the National High School Sports-Related Injury Surveillance Study. Data of athletic exposures, dental injuries, mouthguard usage, and mechanism of injury from the 2005/2006 to the 2019/2020 academic years were analyzed. RESULTS: During the study period, there were 459 dental injuries in 49,987,927 athletic exposures resulting in a dental injury rate of 0.9 per 100,000 athletic exposures (AE). Slightly more than half of the traumatic dental injuries were sustained during competition (n = 256; 55.8%) and the rest (n = 200; 43.6%) were sustained during practice. The rate of dental injury in competition was 3.6 times higher than the rate in practice (RR: 3.6, 95% CI: 3.0-4.4). Dental injuries comprised 0.4% of the total 108,574 injuries sustained by athletes. Among girls' sports, field hockey had the highest rate (3.5 per 100,000 AE) and among boys' sports, basketball (2.4 per 100,000 AE) had the highest rate of dental injury. The most common mechanism of injury was contact with another player (276; 60.4%) followed by contact with apparatus (146; 31.9%). In the majority of dental injuries (308; 75.1%), the athlete was not wearing a mouthguard when the dental injury was sustained. CONCLUSIONS: Dental injuries were a small proportion of all injuries sustained by high school athletes. The majority of dental injuries were sustained when the athlete was not wearing a mouthguard.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats / Mitigação da nefrotoxicidade induzida pela cisplatina pela casticina em ratos albinos machos

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-κB), fator de necrose tumoral-α (TNF-α), interleucina-1β (IL-1β), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats

Abstract Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-B), tumor necrosis factor- (TNF-), Interleukin-1 (IL-1), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Resumo A cisplatina (CP) é uma droga antineoplásica poderosa, comumente usada, com vários efeitos colaterais. Casticin (CAS) é considerado um eliminador de radicais livres e um potente antioxidante. A presente pesquisa foi planejada para avaliar o potencial curativo da CAS em lesão renal induzida por PC em ratos albinos machos. Vinte e quatro ratos albinos machos foram distribuídos em quatro grupos iguais. O Grupo 1 foi considerado grupo controle. Os animais do Grupo 2 foram injetados com 5 mg / kg de PB por via intraperitoneal. O Grupo 3 foi cotratado com CAS (50 mg / kg) por via oral e injeção de CP (5 mg / kg). O Grupo 4 foi tratado com CAS (50 mg / kg) por via oral durante todo o experimento. A administração de CP reduziu substancialmente as atividades de catalase (CAT), superóxido dismutase (SOD), peroxidase (POD), glutationa S-transferase (GST), glutationa redutase (GSR), glutationa (GSH), enquanto aumentou as substâncias reativas ao ácido tiobarbitúrico (TBARS) e níveis de peróxido de hidrogênio (H2O2). Os níveis de ureia, creatinina urinária, urobilinogênio, proteínas urinárias, molécula 1 de lesão renal (KIM-1) e lipocalina associada à gelatinase de neutrófilos (NGAL) aumentaram substancialmente. Em contraste, a albumina e a depuração da creatinina foram significativamente reduzidas no grupo tratado com PC. Os resultados demonstraram que a CP aumentou significativamente os indicadores de inflamação, incluindo fator nuclear kappa-B (NF-B), fator de necrose tumoral- (TNF-), interleucina-1 (IL-1), interleucina-6 (IL-6) níveis e atividade da ciclooxigenase-2 (COX-2) e danos histopatológicos. No entanto, a administração de CAS apresentou um efeito paliativo contra a toxicidade renal gerada por CP e recuperou todos os parâmetros, trazendo-os a um nível normal. Estes resultados revelaram que o CAS é um composto eficaz com potencial curativo para combater o dano renal induzido por CP.

Primary Second Molar Treatment as a Predictor of Repeat General Anesthesia.

Purpose: The purpose of this study was to investigate an association between treatments on the primary second molars (PSMs) under general anesthesia (GA) and odds of repeat GA. Methods: This was a retrospective study of children who received dental treatment under GA between the ages of 24 to 48 months. Descriptive statistics and logistic regression models (P<0.05) were used to test the association between the treatment of PSMs at the first dental GA visit (GA1) and the odds of receiving GA a second time (GA2) within the next 55 months post-GA1. Results: A total of 819 children (53 percent male) with a mean (±SD) age of 36 (±seven SD) months and 3,276 PSMs were included. Only three percent of children with all PSMs covered at GA1 received GA2. The odds of GA2 significantly increased for children with any uncovered PSMs. Among children with four uncovered PSMs, 19 percent (odds ratio [OR] equals 13; 95 percent confidence interval [95% CI] equals 5.8 to 33.5; P<0.001) and among those with unerupted PSMs at GA1, 51 percent received GA2 (OR equals 62.9; 95% CI equals 23.5 to 189.2; P<0.001). In the group that received GA2, 79.1 percent of uncovered PSMs at GA1 eventually received a stainless steel crown at GA2. Conclusions: Restorative treatments other than stainless steel crowns were associated with higher odds of repeat general anesthesia. These findings support the preferential use of full-coverage restorations for the treatment of carious primary molars in young children undergoing GA to minimize the risk of the need for repeat GA.

Mitigation of cisplatin induced nephrotoxicity by casticin in male albino rats.

Cisplatin (CP) is a commonly used, powerful antineoplastic drug, having numerous side effects. Casticin (CAS) is considered as a free radical scavenger and a potent antioxidant. The present research was planned to assess the curative potential of CAS on CP persuaded renal injury in male albino rats. Twenty four male albino rats were distributed into four equal groups. Group-1 was considered as a control group. Animals of Group-2 were injected with 5mg/kg of CP intraperitoneally. Group-3 was co-treated with CAS (50mg/kg) orally and injection of CP (5mg/kg). Group-4 was treated with CAS (50mg/kg) orally throughout the experiment. CP administration substantially reduced the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione reductase (GSR), glutathione (GSH) content while increased thiobarbituric acid reactive substances (TBARS), and hydrogen peroxide (H2O2) levels. Urea, urinary creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, albumin and creatinine clearance was significantly reduced in CP treated group. The results demonstrated that CP significantly increased the inflammation indicators including nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1ß (IL-1ß), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activity and histopathological damages. However, the administration of CAS displayed a palliative effect against CP-generated renal toxicity and recovered all parameters by bringing them to a normal level. These results revealed that the CAS is an effective compound having the curative potential to counter the CP-induced renal damage.

Slipped Capital Femoral Epiphysis Associated With Vitamin C Deficiency in a 7-year-old Boy.

Scurvy is rare in the present world and is mostly found in children with abnormal dietary habits and physical and mental disabilities. Scurvy can present in various forms, mimicking several common diseases, thus making the diagnosis difficult. Spontaneous epiphyseal separation is known to occur in scurvy, although rarely reported. The usual locations of these epiphyseal separations are distal femur and proximal humerus. Our case is unique in that scurvy in a seemingly normal child resulted in proximal femur epiphyseal separation which was not reported previously. We report a case of a 7-year-old boy presenting with pain and swelling in multiple joints for 6 months and later inability to walk. Pseudoparalytic frog-leg posture, dietary history of selective eating, and typical radiologic features made us consider a diagnosis of scurvy which was confirmed by a low serum vitamin C level. He developed epiphyseal separation of proximal femur and was treated with percutaneous screw fixation. Vitamin C supplementation resulted in prompt improvement clinically and radiologically.

The association between traumatic dental and brain injuries in American children.

BACKGROUND/AIM: It is crucial that dentists who treat traumatic dental injuries rule out concomitant brain injuries. Despite anatomic proximity, controversy exists regarding association between facial trauma and head injury. The aim of this study was to examine the association between dento-alveolar trauma (DAT) and traumatic brain injuries (TBI) using a national dataset of emergency department (ED) visits. MATERIAL AND METHODS: Nationwide Emergency Department Sample (NEDS) data, one of the Healthcare Cost and Utilization Project (HCUP) datasets, were analyzed. Encounters of patients age 0-18 years with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes associated with DAT and TBI in the 2010-2014 NEDS were identified. Data were analyzed using descriptive statistics, chi-square test, and logistic regression models to investigate the association between DAT and TBI and factors associated with TBI in DAT-positive patients. RESULTS: During the study period, 6 281 658 ED visits were associated with traumatic injuries. DAT was recorded in 93 408 (1.5%) and TBI was recorded in 996 334 (15.9%) of these traumatic injury visits. Within the group of DAT-positive encounters, 7035 (7.5%) had codes associated with TBI. Of trauma encounters where a DAT was not involved (6 188 250 encounters), 989 299 (16%) had an associated TBI code. Patients with DAT had 0.20 odds of having TBI (95% CI, 0.19-0.20, P < .0001) compared with patients who did not have DAT when all other confounding variables were kept constant. Having multiple injuries, being involved in motor vehicle crashes, and injuries due to assault were associated with higher odds of concomitant TBI in patients who sustained DAT. CONCLUSIONS: There was an inverse association between DAT and TBI in this study population.

Advances in Antimicrobial Microneedle Patches for Combating Infections.

Skin infections caused by bacteria, viruses and fungi are difficult to treat by conventional topical administration because of poor drug penetration across the stratum corneum. This results in low bioavailability of drugs to the infection site, as well as the lack of prolonged release. Emerging antimicrobial transdermal and ocular microneedle patches have become promising medical devices for the delivery of various antibacterial, antifungal, and antiviral therapeutics. In the present review, skin anatomy and its barriers along with skin infection are discussed. Potential strategies for designing antimicrobial microneedles and their targeted therapy are outlined. Finally, biosensing microneedle patches associated with personalized drug therapy and selective toxicity toward specific microbial species are discussed.

A survival analysis of primary second molars in children treated under general anesthesia.

BACKGROUND: The authors examined time to need new treatment of primary second molars in very young children treated under general anesthesia (GA). METHODS: During this retrospective chart review, the authors examined patients aged 2 through 4 years with severe early childhood caries (ECC) who received dental treatment under GA. Primary second molars were tracked in periodic recall visits after GA for 6 through 89 months. Using a random-effects Cox proportional hazards model, the authors compared hazards of teeth requiring new treatment based on treatments received at GA. RESULTS: Of 3,166 primary second molars included in the study, 367 (12%) were not erupted, 77 (2%) received topical fluoride only, 873 (28%) received a pit and fissure sealant, 242 (8%) received a composite restoration, and 1,607 (50%) received a stainless steel crown (SSC) at GA. SSCs had a survival probability of 98% by 84 months after GA, significantly higher than all other groups (P < .0001). The second molars that were not erupted at GA had the highest hazard, especially within the first 24 months after GA. Teeth that received sealant had longer time to need new treatment than nonsealed teeth; however, at 84 months after GA, only 33% of the sealed teeth did not require additional treatment. CONCLUSIONS: Preventive or restorative treatments other than SSCs resulted in need for new treatment in a substantial number of teeth. SSCs had the highest success in this population with severe ECC treated under GA and should be chosen over other restorative options to reduce risk of undergoing repeat dental treatment. PRACTICAL IMPLICATIONS: Aggressive treatment with SCC should be considered for young children with severe ECC especially those who are treated under GA at a young age.

SKINTED: A Rare Complication After Total Knee Arthroplasty.

BACKGROUND: Surgery of the knee, injury to the infrapatellar branch of the saphenous nerve, traumatic eczematous dermatitis is a neuropathic dermatitis specific to total knee arthroplasty (TKA), occurring around the healed surgical scar area. Very few case reports exist in orthopaedic literature regarding this rare skin complication after TKA. We report a series of cases and estimated the incidence of this condition in our institute. METHODS: During the 1-year period from January 2018 to December 2018, patients who have undergone TKA and later presented with skin lesions adjacent to the operated site were identified. Detailed history was taken, and full clinical examination was performed for all the reported cases. RESULTS: A total of 9 lesions in 8 patients were identified out of a total of 203 consecutive TKAs operated during the study period, with an estimated incidence of 4.4%. The mean age was 64 years (range, 58-78 years). The mean time from surgery to diagnosis was 4 months (range, 3-6 months). CONCLUSIONS: This group of dermatitis caused due to surgical transection of the infrapatellar branch of the saphenous nerve during TKA is a rare cutaneous complication, with an estimated incidence of 4.4% from this study. Lesions typically appear lateral to the operative scar within an area of hypoesthesia. Lesions in all patients improved after topical steroid therapy with no recurrences at further follow-up. Arthroplasty surgeons should have awareness of this benign complication, thereby avoiding unwarranted additional workup and alleviating unnecessary psychological stress to the patient.

A Comparison of the Central versus Peripheral Gastrointestinal Prokinetic Activity of Two Novel Ghrelin Mimetics.

The gastrointestinal (GI) prokinetic effects of ghrelin occur through direct peripheral effects on ghrelin receptors within the enteric nervous system and via the ghrelin receptor on the vagus nerve, which activate a centrally mediated mechanism. However, the relative contribution of peripheral versus central effects to the overall prokinetic effect of ghrelin agonists requires further investigation. Here, we investigated the central versus peripheral prokinetic effect of ghrelin by using two novel ghrelin agonists: HM01 (N'-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-N-methyl-N-[1,3,3-trimethyl-(4R)-piperidyl]-urea HCL) with high brain penetration compared with HM02 (N'-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-N-hydroxy-N-(1-methyl-4-piperidinyl)-urea), a more peripherally acting ghrelin agonist. The pharmacokinetic profiles of both ghrelin agonists were evaluated after intravenous and oral administration in rats. The efficacy of HM01 and HM02 was assessed in a rat model of postoperative ileus (POI) induced by abdominal surgery and in a rodent defecation assay. Pharmacokinetic results in our models confirmed that HM01, but not HM02, was a brain-penetrant ghrelin agonist. Administration of either HM01 or HM02 reversed the delayed upper and lower gastrointestinal transit induced by abdominal surgery to levels resembling the non-POI controls. In the defecation test, HM01, but not HM02, significantly increased the weight of fecal pellets. Our findings suggest that, in a rodent model of POI, synthetic ghrelin agonists stimulate GI transit through a peripheral site of action. However, in the defecation assay, our data suggest that a ghrelin-mediated mechanism is located at a central site. Taken together, a ghrelin agonist with both central and peripheral prokinetic activity may show therapeutic potential to treat delayed GI transit disorders.

Linaclotide Attenuates Visceral Organ Crosstalk: Role of Guanylate Cyclase-C Activation in Reversing Bladder-Colon Cross-Sensitization.

Bladder pain syndrome (BPS) is poorly understood; however, there is a female predominance and comorbidity with irritable bowel syndrome (IBS). Here we test the hypothesis that linaclotide, a guanylate cyclase-C (GC-C) agonist approved for the treatment of IBS with constipation (IBS-C), may represent a novel therapeutic for BPS acting through a mechanism involving an inhibition of visceral organ cross-sensitization. We showed previously that infusion of dilute protamine sulfate (PS) into the bladder increased sensitivity and permeability in the bladder and colon. PS was infused into the bladder of female rats; sensitivity was assessed via application of von Frey filaments applied to the suprapubic area and the frequency of withdrawal responses was recorded. Colonic sensitivity was measured via visceromotor behavioral response to graded pressures of colorectal distension (CRD). Permeability was measured in vitro via transepithelial electrical resistance (TEER) and conductance (G). Linaclotide (3 µg/kg, p.o.) or vehicle was administered daily for 7 days prior to experiments. Rats treated with PS bladder infusion exhibited visceral hyperalgesia, as shown by a significantly higher response frequency to individual von Frey filaments and increased behavioral responses to CRD. Linaclotide attenuated bladder and colonic hyperalgesia to control levels. PS infusion into the bladder increased bladder and colon permeability measured as a decrease in TEER and increased G. Linaclotide significantly inhibited PS-induced colonic hyperpermeability while having no effect on bladder hyperpermeability. Our findings suggest a novel treatment paradigm for GC-C agonism in IBS-C and BPS mediated through a mechanism involving visceral organ crosstalk.

Lack of Association between NOD2 rs3135500 and IL12B rs1368439 microRNA Binding Site SNPs and Colorectal Cancer Susceptibility in an Iranian Population.

OBJECTIVE: The purpose of this study was to evaluate the potential association between single nucleotide polymorphisms (SNPs) in microRNA (miRNA) binding sites in the NOD2 and IL12B gene 3.-untranslated regions and colorectal cancer (CRC) susceptibility in an Iranian population. METHODS: We genotyped NOD2 rs3135500 [3. untranslated region (UTR) A/G] and IL12B rs1368439 (3.UTR G /T) in a hospital-based study of 92 colorectal cancer cases and 105 healthy controls. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from FFPE tissue and peripheral blood. RESULTS: our results showed similar distribution of genotype and allelic frequencies of the NOD2 and IL12B polymorphisms between patients and controls. When the more common rs3135500 AA genotype was used as the reference, the rs3135500 AG and rs3135500 GG genotypes were not significantly associated with the risk of CRC (OR = 1.294, 95% CI: 0.524 -3.197; and OR = 2.230, 95% CI: 0.87 - 5.715, respectively), and The IL12B rs1368439 TG and IL12B rs1368439 GG genotypes were not significantly associated with the risk of CRC compared with the IL12B rs1368439 TT genotype (OR = 1.547 95% CI: 0.187- 12.771; and OR = 1.753, 95% CI: 0.217-14.157, respectively). CONCLUSION: NOD2 rs3135500 and IL12B rs1368439 SNPs were not genetic risk factors for colorectal cancer in the studied Iranian population.

Ectopic pregnancy: an analysis of 62 cases.

Sixty-two cases of ectopic pregnancy admitted in the Department of Obstetrics and Gynaecology, Jinnah Postgraduate Medical Centre, Karachi from July, 1989 to December, 1990 were analysed to determine the incidence, risk factors, diagnostic features and management. During this period a total number of 10,798 patients were delivered giving an incidence of 1:174 births or 5.7 per 1000 births. In 48.3% cases the cause was unknown, 16.1% followed by pelvic inflammatory disease, 16.1% had history of D & E for abortion, 6.4% had history of different type of pelvic surgery, 4.8% had IUCD in situ, 1.6% had recurrent ectopic pregnancy. Diagnosis was made clinically in 80.6% cases. Culdocentesis was performed in all cases except one and was diagnostic in 90.1% cases. Ultrasound was performed in 51 cases and showed positive results in 90.1% cases. Laparoscopy was performed in only 10 cases and had 100% accurate results. After thorough re-suscitation laparotomy was performed in all cases. Partial salpingectomy was done in 53.2%, salpingectomy and tubal ligation in 32.2%. (They had already completed their family) and salpingo-oophorectomy in 4.8% cases. Tubes were conserved in 6.2% cases (all of them were primigravidas). In single abdominal pregnancy, dead fetus and placenta was removed from the peritoneal cavity very carefully. The mortality rate in this study was 1.6%.