Dermal Template for Superficial Defects Related to Intra Oral Malignancy.

Flaps are the workhorse reconstructive options for management of defects for oral malignancy. Superficial defects are traditionally managed with skin grafting or healing by secondary intention, each of which have its own problems. We would like to share our experience of use of dermal template for superficial intra oral defects related to oral malignancy. Patients with cancerous and pre-cancerous lesions which resulted in defects involving mucosa and superficial muscles were included in the study. All the patients were managed with Matriderm 2 mm dermal template without the use of skin graft/ flap. 7 patients in the period of 6 months with superficial defects were managed with Matriderm alone. Two patients had lesions on the tongue while five had it on Buccal mucosa. None of these patients had post operative pain, contracture or trismus. Speech and swallowing at 6 month average follow up is normal. Dermal Substitutes are effective method of management of superficial intra oral defects with no donor area morbidity.

Colorectal Adenocarcinoma Derived From Mature Cystic Teratomas: A Case Report With Review of the Literature.

Mature cystic teratomas (MCTs) are the most common benign ovarian germ cell neoplasms in women of reproductive age. Rarely, somatic malignancies arise from MCTs, the most common being squamous cell carcinoma. Adenocarcinomas are less common and colorectal adenocarcinomas are extremely rare. We present a case of somatic adenocarcinoma of colorectal type which may pose challenges in diagnosis and treatment. A middle-aged female presented to the Emergency Department with lower abdominal pain. CT scan revealed an 11 cm sharply demarcated left pelvic mass. Laparoscopy showed a left ovarian mass with torsion, a smooth external surface, and thick brownish contents. An intraoperative evaluation was consistent with an adenocarcinoma. Permanent histopathology revealed adenocarcinoma of colorectal phenotype with necrosis. Additional evaluation of the cyst showed benign colonic epithelial lining. The immunohistochemistry (IHC) profile of positive CDX2 and CK20 and negative PAX8, CK7, ER, and PR suggested a colorectal-type somatic adenocarcinoma arising from the MCT and was staged as IA, after negative endoscopic findings. Due to their rarity and atypical symptoms, distinguishing metastatic tumors from MCT-derived somatic malignancies is a challenging process. CT scan and serum tumor markers can be helpful but are not definite. Thorough clinical evaluation and proper staging are necessary after pathologic evaluation. Extensive sampling and IHC can further characterize the origin of the tumor. Diligent sampling and a high index of suspicion in this case clinched the correct diagnosis and clinical management. The patient is being treated for stage IA ovarian cancer as opposed to stage IV metastatic colorectal cancer.

False positive urine amphetamine immunoassay due to solriamfetol.

Solriamfetol is a schedule IV-controlled substance used to treat excessive daytime sleepiness resulting from narcolepsy or obstructive sleep apnea. We present a patient prescribed solriamfetol who tested positive for amphetamines on a routine urinary toxicology screen despite patient denial of illicit drug use, raising the possibility of a false positive amphetamine screen. Spiking studies were performed on negative urine, and different concentrations of solriamfetol drug on 2 different amphetamine assays: the commonly used Beckman Emit® II Plus Amphetamines Assay, and the Citrine™ Triple Quad™ MS/MS Systems. The Beckman yielded positive results for amphetamines at solriamfetol concentrations of 200 µg/mL and 2000 µg/mL and negative results at 0.2 µg/mL and 2 µg/mL. However, the Citrine™ Triple Quad™ MS/MS Systems was negative at all concentrations. The Beckman Emit® II Plus Amphetamine Assay gave false positive results for amphetamines due to solriamfetol drug usage, a finding of relevance to prescribers of solriamfetol.

Effects of Exercise Frequency with Complex Contrast Training on Measures of Physical Fitness in Active Adult Males.

Complex contrast training (CCT) is an exercise modality that utilizes both high-load resistance activity and low-load plyometric activity in a set-by-set fashion within a single exercise session. Such a combination of exercises targets multiple aspects of the force−velocity curve and may thus lead to improvement of various components of physical fitness. However, no previous study has attempted to compare the effects of load-equated two vs. three CCT sessions per week on measures of physical fitness. Forty-five male participants aged 21.4 ± 2.0 years were randomly assigned to either two weekly CCT sessions (CCT-2; n = 15), three weekly CCT sessions (CCT-3; n = 15), or an active control group (CG; n = 15). Selected measures of physical fitness were assessed pre- and post-six weeks of training. The tests included the assessment of 15 and 30 m linear sprint speeds, upper (medicine ball throw) and lower limb muscle power (standing long jump and countermovement jump with arm thrust), muscle strength (isokinetic peak knee extensor/flexor torque), and change-of-direction speed (modified agility T-test (MAT)). Significant group−time interactions were observed for all dependent variables (all p < 0.001, ɳp2 = 0.51−0.78) using ANOVA. Post hoc tests indicated significant performance improvements for the CCT-2 and CCT3 groups for all dependent variables (Hedge's g = 0.28−3.26, %Δ = 2.4−16.7), including the 15 and 30 m linear sprint speeds (p < 0.001), medicine ball throw (p < 0.001), standing long jump (p < 0.001), countermovement jump with arm thrust (p < 0.001), right leg knee extensor (p < 0.001) and flexor peak torque (p < 0.001), left leg knee extensor (p < 0.001) and flexor peak torque (p < 0.001), and change-of-direction speed (p < 0.001). The CCT-3 group showed greater improvements in MAT compared to the CCT-2 group (g = 3.26 vs. 0.70, p < 0.001). In conclusion, compared to active controls, the load-equated CCT-2 and CCT-3 programs provided similar effects on measures of physical fitness in active adult males. However, an athlete's goal is to improve their MAT score, the CCT-3 program may elicit greater improvements compared with the CCT-2 program.

Estimation of salivary lactate dehydrogenase in oral squamous cell carcinoma, oral leukoplakia, and smokers.

Introduction: Lactate dehydrogenase (LDH) is an enzyme seen within every cell during their normal metabolic function. It is always confined within the cell cytoplasm and it becomes extracellular only when a cell dies. The extracellular presence of LDH is related to cell necrosis and tissue breakdown. Therefore, we designed a study to estimate and compare LDH levels in the saliva of patients with oral cancer, oral leukoplakia (OL), and smokers without lesions and in controls. Materials and Methods: A total of 81 subjects of both genders, between the ages of 20 and 70 years, were included in the study. The study group was divided into four: group I-controls (n = 20), Group II-smokers (n = 20), Group III-subjects with OL (n = 20), and Group IV-subjects with oral squamous cell carcinoma (OSCC) (n = 21). Five milliliters of unstimulated salivary sample was collected from each participant, and salivary LDH level was measured. The obtained values were tabulated and statistically analyzed. P < 0.05 was considered to be statistically significant. Results: The difference in LDH levels among the four groups was found to "BE" statistically significant. LDH values showed a marked increase in the leukoplakia group (49.79 ± 19.88 IU/L) and OSCC group (106.97 ± 32.75 IU/L) when compared to controls and smokers. Conclusion: We found that salivary LDH was increased in patients with leukoplakia and OSCC. Smoking alone did not produce any alterations in salivary LDH. It is possible that salivary LDH could be a potential biomarker to identify early premalignant or malignant changes in smokers.

Maternal oxytocin administration modulates gene expression in the brains of perinatal mice.

OBJECTIVES: Oxytocin (OXT) is widely used to facilitate labor. However, little is known about the effects of perinatal OXT exposure on the developing brain. We investigated the effects of maternal OXT administration on gene expression in perinatal mouse brains. METHODS: Pregnant C57BL/6 mice were treated with saline or OXT at term (n=6-7/group). Dams and pups were euthanized on gestational day (GD) 18.5 after delivery by C-section. Another set of dams was treated with saline or OXT (n=6-7/group) and allowed to deliver naturally; pups were euthanized on postnatal day 9 (PND9). Perinatal/neonatal brain gene expression was determined using Illumina BeadChip Arrays and real time quantitative PCR. Differential gene expression analyses were performed. In addition, the effect of OXT on neurite outgrowth was assessed using PC12 cells. RESULTS: Distinct and sex-specific gene expression patterns were identified in offspring brains following maternal OXT administration at term. The microarray data showed that female GD18.5 brains exhibited more differential changes in gene expression compared to male GD18.5 brains. Specifically, Cnot4 and Frmd4a were significantly reduced by OXT exposure in male and female GD18.5 brains, whereas Mtap1b, Srsf11, and Syn2 were significantly reduced only in female GD18.5 brains. No significant microarray differences were observed in PND9 brains. By quantitative PCR, OXT exposure reduced Oxtr expression in female and male brains on GD18.5 and PND9, respectively. PC12 cell differentiation assays revealed that OXT induced neurite outgrowth. CONCLUSIONS: Prenatal OXT exposure induces sex-specific differential regulation of several nervous system-related genes and pathways with important neural functions in perinatal brains.

Association of psychosocial factors with aggression among school going rural adolescents in Haryana.

BACKGROUND: Adolescents are being involved in aggressive activities nowadays. Sometimes, involvement in aggressive activities may be fatal for the victim as well as for the doer. It is a matter of great concern for all including parents, teachers, psychologists, social reformers, and others. A momentary expression of anger sometimes may spoil the future life of the adolescents. AIM AND OBJECTIVES: To determine the prevalence of aggression and to identify the psychosocial risk factors associated with aggression among school-going adolescents. METHODOLOGY: The study recruited 480 school-going rural adolescents from eight government senior secondary schools in the rural block of Beri, district Jhajjar (Haryana). OBSERVATIONS: The mean age of the adolescents was 14.11 ± 1.12 years; 49.4% of the adolescents were found to be aggressive. After applying binary logistic regression, there was a statistically significant relation between aggression and determinants like class, gender, occupation of the father. CONCLUSION AND RECOMMENDATIONS: The study concluded that determinants like age, class of students, gender of the subject, occupation of father found a significant association with aggression. To solve this current situation, parents must give love, attention to their children and must act in an appropriate way in front of them and be role models.

Inter-Limb Jump Asymmetries and Their Association with Sport-Specific Performance in Young Male and Female Swimmers.

This study aimed to examine inter-limb jump asymmetries and their association with sport-specific performance in young swimmers. Thirty-eight (male, n = 19; female, n = 19) regional/national level young swimmers (age: 12.3 ± 1.2 years; height: 159.6 ± 8.2 cm; body mass: 52.5 ± 9.2 kg) participated in this study. Inter-limb asymmetries were assessed for single-leg countermovement jump (SLCMJ) and single-leg standing long jump (SLSLJ). Sport-specific performance was evaluated using front crawl (i.e., 50 m and 25 m) and front crawl kick (i.e., 50 m and 25 m). The kappa coefficient revealed a "slight" level of agreement (Κ = 0.156, 0.184, and 0.197 for female, male, and all, respectively) between the direction of asymmetry for SLCMJ and SLSLJ, indicating that asymmetries rarely favored the same limb during both tests. A paired sample t-test showed a significant difference (p = 0.025) between asymmetry scores obtained in SLCMJ and SLSLJ. No significant difference was found in asymmetry scores between males and females (p = 0.099 to 0.977). Additionally, no association between asymmetry scores and sport-specific performance was observed (p > 0.05). Our findings highlight the independent nature of inter-limb asymmetries derived from SLCMJ and SLSLJ among young male and female swimmers. Further, our results suggest no association between jumping asymmetries and sport-specific performance.

Developing complex odontoma in a 4-year-old child with active ameloblastic follicles: A case report.

The World Health Organization (WHO) classification of odontogenic tumors, in its different iterations, has seen several modifications in benign mixed odontogenic tumors. Odontoma is a benign mixed odontogenic tumor that shows dental hard tissue formation to varying degrees. Although odontomas are the most common odontogenic tumors, they are mostly seen in the form of compound odontomas, where the dental hard tissues resemble tooth-like structures. Complex odontoma shows a haphazard mass of dental hard tissues and is generally identified at an older age (mean age of around 20 years). Incidence of complex odontoma in very young children is quite rare, with only around 10 cases associated with the primary dentition being reported in the literature till date. Unlike other odontomas, our case showed an active epithelial component in the form of tooth buds and ameloblastic follicles along with the hard tissues, which made it difficult to distinguish from other similar lesions like ameloblastic fibroma with hard tissue formation and ameloblastoma arising from an odontoma. This article reports the 11th case of complex odontoma associated with the primary dentition, and the youngest such case to be reported in the Indian population.

Analysis of factors determining thermal changes at osteotomy site in dental implant placement - An in-vitro study.

BACKGROUND: Heat generation during osteotomy site preparation is a crucial factor that determines the success of dental implant placement. Among the factors that affect the heat generation, drilling speed, hand pressure and coolant temperature are independent variables. However, a relation between these three parameters and their optimal values required for the maximum outcome has not been studied so far. This study aims at finding out a relation between these factors in order to derive the optimum balance required, using an in vitro study. MATERIAL AND METHODS: This in vitro experiment was performed on bovine femur. A total of 72 drillings were undertaken with the aid of a physiodispenser mounted on the test apparatus. Drill diameters of 2 mm and 2.8 mm, rotated at 1500, 2000 and 2500 rpm were included for the analysis. Hand pressures included for the comparison were 1.2 kgf and 2.4 kgf. Normal saline at room temperature, and that chilled to 00C were used for external irrigation. The temperature generated during drilling was recorded by infrared thermography using a Forward-Looking Infrared (FLIR) camera. RESULTS: The highest temperature during osteotomy was observed at 2000 rpm rotational speed, 1.2 kgf operator hand pressure and saline irrigant solution at room temperature. In contrast, the lowest temperature generated was using 2500 rpm rotational speed, 2.4 kgf operator hand pressure and chilled irrigant solution. CONCLUSIONS: The results indicate that none of the three experimented parameters generated heat above the critical temperature for bone necrosis (47°C). Thus, a high drilling speed with high hand pressure and continuous irrigation with copious amounts of cooled saline may be the ideal combination for implant osteotomy site preparation. Key words:Heat generation, dental implant drills, drilling speed, drilling pressure, irrigation, infrared thermography, thermal necrosis, osteotomy preparation.

Magnesium deficiency with high calcium-to-magnesium ratio promotes a metastatic phenotype in the CT26 colon cancer cell line.

Magnesium (Mg) plays important roles in maintaining genomic stability and cellular redox. Mg also serves as nature's physiological calcium (Ca) channel antagonist, controlling intracellular Ca entry. Because Ca is the most important second messenger, its intracellular concentration is tightly regulated. Excess intracellular Ca can activate aberrant signaling pathways leading to the acquisition of pathological characteristics and cell injury. Several epidemiological studies have linked Mg deficiency (MgD) and increased Ca:Mg ratios with higher incidences of colon cancer and increased mortality. While it is estimated that less than 50% of the US population consumes the recommended daily allowance for Mg, Ca supplementation is widespread. Therefore, we studied the effect of MgD, with variable Ca:Mg ratios on cellular oxidative stress, cell migration, calpain activity, and associated signaling pathways using the CT26 colon cancer cell line. MgD (with Ca:Mg ratios >1) elevated intracellular Ca levels, calpain activity and TRPM7 expression, as well as oxidative stress and cell migration, consistent with observed degradation of full-length E-cadherin, ß-catenin, and N-terminal FAK. MgD was accompanied by enhanced degradation of IκBα and the transactivation domain containing the C-terminus of NF-κB p65 (RelA). MgD-exposed CT26 cells exhibited increased p53 degradation and aneuploidy, markers of genomic instability. By contrast, these pathological changes were not observed when CT26 were cultured under MgD conditions where the Ca:Mg ratio was kept at 1. Together, these data support that exposure of colon cancer cells to MgD with physiological Ca concentrations (or increasing Ca:Mg ratios) leads to the acquisition of a more aggressive, metastatic phenotype.

Association between the socioeconomic determinants and soil-transmitted helminthiasis among school-going children in a rural area of Haryana.

BACKGROUND: WHO indicates that India has the highest burden of soil-transmitted helminthiasis (STH) in the world, contributing to 25% of the total global cases, with 220 million children aged 1-14 estimated to be at risk. AIM AND OBJECTIVE: To study the association between the socioeconomic factors and STHs among primary school children in a rural area of Haryana. METHODOLOGY: The study was conducted among children aged 6-10 years studying in the rural government primary schools in the rural areas of Haryana. A total of 300 children were enrolled from government school. RESULTS: The study found that the prevalence of helminthiasis was 28.7% (86/300) and of these 14.0% children were infected with Ascaris lumbricoides and sex wise association with Helminthic infection was observed as statistically nonsignificant. One third of the (31.39%; 27/86) children were pallor and 5.81% subjects were having Bitot's spot while 13.95% children were having constitutional symptoms such as weakness, 6.97% subjects have fatigue, and 5.81% children have body ache. DISCUSSION: The morbidity can be reduced with appropriate inputs to improve the environmental factors. This may need investment for sanitary latrines, food hygiene, and safe drinking water, anti-helminthic drugs, and health education. CONCLUSION AND RECOMMENDATIONS: The results of the study concluded and recommended that proper implementation of national deworming day and other long-term strategies like sanitation, clean drinking water, adequate sanitation, and also improvement in nutritional status through various nutritional health programmes.

Impact of Trust and Privacy Concerns on Technology Acceptance in Healthcare: An Indian Perspective.

This paper augments the technology acceptance model (TAM) by empirically investigating the influence of behavioral traits (privacy concerns and trust) and cognitive beliefs (perceived usefulness and perceived ease of use) on patients' behavioral intention to accept technology in healthcare service delivery. Despite increased emphasis on healthcare service delivery, there has been limited studies as to how various behavioral constructs are related to adoption of new technology in healthcare sector. To this end, and to develop meaningful insights, a conceptual model integrating behavioral constructs with constructs related to technology acceptance model is devised. The aim here is essentially to understand relationships that predict patients' acceptance of technology in healthcare services. The devised model is tested on responses obtained from survey of 416 patients availing healthcare service at various primary health centers in New Delhi, India. Structural equation modeling (SEM) is employed to conceptualize the model and validate nine hypotheses entailing key constructs. The results indicate that perceived usefulness, perceived ease of use, trust and privacy concern are direct predictors of patients' behavior to accept technology in availing healthcare services. In summary, this research provides an empirical contribution to the literature on effect of trust and privacy concerns on acceptance of technology in healthcare.

Effect of Inhalational Therapy on Buccal Mucosal Cells in Asthmatic Patients: A Cytological Study.

OBJECTIVE: Inhalational drugs used in treating asthma have several side effects including those on oral tissues. We therefore designed a study to analyze the effects of inhalational drugs on the buccal mucosal cells of the oral cavity. METHODS: Smears were obtained from clinically normal buccal mucosa of 20 randomly selected asthmatic patients who had been under inhalational therapy for at least 6 months. The Papanicolaou-stained smears were then analyzed for average nuclear area, average cytoplasmic area, and average nuclear area:cytoplasmic area ratio for each patient, and the values were compared with those of 10 healthy controls. RESULTS: A statistically significant decrease in cytoplasmic area (P<0.001) was found in asthmatic patients compared to controls. A significant increase in mean nuclear area:cytoplasmic area ratio (P<0.001) was noted in asthmatic patients when compared to controls. CONCLUSION: Prolonged use of inhalational drugs in patients diagnosed with asthma is associated with changes in oral epithelial cells. There is a need to assess whether these are the direct adverse effects of such drugs and whether they have any long-term impact on oral tissues.

Pattern and determinants of soil-transmitted helminthiasis in a rural area of Haryana: A school-based study.

BACKGROUND: In the world, helminthiasis is the major public health problem in school-age children. More than 60 million school-age children live in intensively transmitted areas and they need immediate treatment and preventive interventions. METHODOLOGY: The study was conducted in the rural government schools of Block Beri, District Jhajjar (Haryana), India, and the study was descriptive and cross-sectional in design. The study recruited 300 school-going children in the age group of 6-10 years. RESULTS: In this study, the mean age of subjects was 7.68 ± 1.467 years and prevalence of soil-transmitted helminths was 28.7%. The association between practice of hand washing and practice of washing fruits and vegetables with helminthic children were found statistically significant. CONCLUSION AND RECOMMENDATION: Impart health education among community through primary care physician about wash hands before eating food and after defecation, washed thoroughly raw and uncooked food before eating.

Immunization Elicits Antigen-Specific Antibody Sequestration in Dorsal Root Ganglia Sensory Neurons.

The immune and nervous systems are two major organ systems responsible for host defense and memory. Both systems achieve memory and learning that can be retained, retrieved, and utilized for decades. Here, we report the surprising discovery that peripheral sensory neurons of the dorsal root ganglia (DRGs) of immunized mice contain antigen-specific antibodies. Using a combination of rigorous molecular genetic analyses, transgenic mice, and adoptive transfer experiments, we demonstrate that DRGs do not synthesize these antigen-specific antibodies, but rather sequester primarily IgG1 subtype antibodies. As revealed by RNA-seq and targeted quantitative PCR (qPCR), dorsal root ganglion (DRG) sensory neurons harvested from either naïve or immunized mice lack enzymes (i.e., RAG1, RAG2, AID, or UNG) required for generating antibody diversity and, therefore, cannot make antibodies. Additionally, transgenic mice that express a reporter fluorescent protein under the control of Igγ1 constant region fail to express Ighg1 transcripts in DRG sensory neurons. Furthermore, neural sequestration of antibodies occurs in mice rendered deficient in neuronal Rag2, but antibody sequestration is not observed in DRG sensory neurons isolated from mice that lack mature B cells [e.g., Rag1 knock out (KO) or µMT mice]. Finally, adoptive transfer of Rag1-deficient bone marrow (BM) into wild-type (WT) mice or WT BM into Rag1 KO mice revealed that antibody sequestration was observed in DRG sensory neurons of chimeric mice with WT BM but not with Rag1-deficient BM. Together, these results indicate that DRG sensory neurons sequester and retain antigen-specific antibodies released by antibody-secreting plasma cells. Coupling this work with previous studies implicating DRG sensory neurons in regulating antigen trafficking during immunization raises the interesting possibility that the nervous system collaborates with the immune system to regulate antigen-mediated responses.

Tissue engineering of human knee meniscus using functionalized and reinforced silk-polyvinyl alcohol composite three-dimensional scaffolds: Understanding the in vitro and in vivo behavior.

Tissue engineered constructs with rapid restoration of mechanical and biological properties remain a challenge, emphasizing the need to develop novel scaffolds. Here, we present a multicomponent composite three-dimensional scaffold structure with biomimetic reinforcement and biomolecule functionalization for meniscus tissue engineering. The scaffold structure was developed using 3:1 silk fibroin (SF) and polyvinyl alcohol (PVA). Autoclaved eggshell membrane (AESM) powder (1-3%w/v) was used as reinforcement to enhance biomechanical properties. Further to improve cell attachment and proliferation, these scaffolds were functionalized using an optimized unique combination of biomolecules. Comprehensive analysis of scaffolds was carried out on morphological, structural, mechanical and biological functionalities. Their mechanical properties were compared with different native human menisci. The results indicated that, functionalized SF-PVA with 3%AESM has shown similar order of magnitude of compressive and dynamic mechanical properties as in human meniscus. Moreover, 3% AESM based scaffolds were found to support better primary human meniscal cellular proliferation and extracellular matrix secretion. Immunohistochemical analysis revealed angiogenesis and biocompatibility with minimal inflammatory response for subcutaneously implanted scaffolds in New Zealand white rabbits. The developed reinforced and functionalized SF-PVA scaffolds can uniquely combine the potential for load-bearing properties with improved in vitro and in vivo support for meniscus tissue regeneration. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1722-1731, 2018.

Activation of the cholinergic anti-inflammatory pathway by GTS-21 attenuates cisplatin-induced acute kidney injury in mice.

Acute kidney injury (AKI) is the most common side effect of cisplatin, a widely used chemotherapy drug. Although AKI occurs in up to one third of cancer patients receiving cisplatin, effective renal protective strategies are lacking. Cisplatin targets renal proximal tubular epithelial cells leading to inflammation, reactive oxygen species, tubular cell injury, and eventually cell death. The cholinergic anti-inflammatory pathway is a vagus nerve-mediated reflex that suppresses inflammation via α7 nicotinic acetylcholine receptors (α7nAChRs). Our previous studies demonstrated the renoprotective and anti-inflammatory effects of cholinergic agonists, including GTS-21. Therefore, we examined the effect of GTS-21 on cisplatin-induced AKI. Male C57BL/6 mice received either saline or GTS-21 (4mg/kg, i.p.) twice daily for 4 days before cisplatin and treatment continued through euthanasia; 3 days post-cisplatin mice were euthanized and analyzed for markers of renal injury. GTS-21 significantly reduced cisplatin-induced renal dysfunction and injury (p<0.05). GTS-21 significantly attenuated renal Ptgs2/COX-2 mRNA and IL-6, IL-1ß, and CXCL1 protein expression, as well as neutrophil infiltration after cisplatin. GTS-21 blunted cisplatin-induced renal ERK1/2 activation, as well as renal ATP depletion and apoptosis (p<0.05). GTS-21 suppressed the expression of CTR1, a cisplatin influx transporter and enhanced the expression of cisplatin efflux transporters MRP2, MRP4, and MRP6 (p<0.05). Using breast, colon, and lung cancer cell lines we showed that GTS-21 did not inhibit cisplatin's tumor cell killing activity. GTS-21 protects against cisplatin-AKI by attenuating renal inflammation, ATP depletion and apoptosis, as well as by decreasing renal cisplatin influx and increasing efflux, without impairing cisplatin-mediated tumor cell killing. Our results support further exploring the cholinergic anti-inflammatory pathway for preventing cisplatin-induced AKI.

Magnesium improves cisplatin-mediated tumor killing while protecting against cisplatin-induced nephrotoxicity.

Approximately 30% of all cancer patients treated with cisplatin, a widely used broad-spectrum chemotherapeutic agent, experience acute kidney injury (AKI). Almost all patients receiving cisplatin have magnesium (Mg) losses, which are proposed to aggravate AKI. Currently, there are no methods to successfully treat or prevent cisplatin-AKI. Whereas Mg supplementation has been shown to reduce AKI in experimental models and several small clinical trials, the effects of Mg status on tumor outcomes in immunocompetent tumor-bearing mice and humans have not been investigated. The purpose of this study was to further examine the effects of Mg deficiency (±Mg supplementation) on cisplatin-mediated AKI and tumor killing in immunocompetent mice bearing CT26 colon tumors. Using a model where cisplatin alone (20 mg/kg cumulative dose) produced minimal kidney injury, Mg deficiency significantly worsened cisplatin-mediated AKI, as determined by biochemical markers (blood urea nitrogen and plasma creatinine) and histological renal changes, as well as markers of renal oxidative stress, inflammation, and apoptosis. By contrast, Mg supplementation blocked cisplatin-induced kidney injury. Using LLC-PK1 renal epithelial cells, we observed that Mg deficiency or inhibition of Mg uptake significantly enhanced cisplatin-induced cytotoxicity, whereas Mg supplementation protected against cytotoxicity. However, neither Mg deficiency nor inhibition of Mg uptake impaired cisplatin-mediated killing of CT26 tumor cells in vitro. Mg deficiency was associated with significantly larger CT26 tumors in BALB/c mice when compared with normal-fed control mice, and Mg deficiency significantly reduced cisplatin-mediated tumor killing in vivo. Finally, Mg supplementation did not compromise cisplatin's anti-tumor efficacy in vivo.