Tissue zinc levels in precancerous tissue in the gastrointestinal tract of azoxymethane (AOM)-treated rats

Alterations in tissue zinc levels have been documented in patients with gastrointestinal tract malignancies and more frequently, in those with colonic cancer. However, the precise role of tissue zinc in carcinogenesis is not well elucidated. This study, using a well-established colon cancer model in rats, was designed to investigate the relationship of tissue zinc to the carcinogenic process. The aim was to examine tissue zinc levels in the preneoplastic tissues and to study the changes that occur during transition of mucosa from normal to preneoplastic state. Six-week old rats were given a single dose subcutaneous injection of azoxymethane (AOM) (30mg/kg body weight) and sacrificed after 1, 2, 5, and 9 months of the treatment. Plasma zinc levels showed a significant decrease (p<0.05) at 9 months compared with controls. Tissue zinc levels showed a significant decrease in the large intestine at 1 and 2 months (p<0.05) and at 5 and 9 months (p<0.01), in the small intestine at 2, 5, and 9 months (p<0.05), and in the stomach at 5 and 9 months (p<0.05). The maximum percent decrease (45%) in tissue zinc was observed in the large intestine at 9 months. Tissue copper zinc super oxide dismutase (CuZnSOD) activity was assessed in the body of the stomach, small intestine, and large intestine and compared with the control group. There was a significant fall in CuZnSOD levels in the small intestine at 9 months (p<0.05) and in the large intestine at 5 and 9 months (p<0.01). Two of these six rats showed histological evidence of precancerous lesions in the mucosa of the colon. This study suggests that the decrease in plasma zinc, tissue zinc and activity of CuZnSOD is associated with development of preneoplastic lesions in the colonic mucosa.     

Fetal liver infusion in aplastic anaemia

Forty patients with severe aplastic anaemia received an intravenous infusion of 0.004 to 11.1 x 10(8) (median: 8 x 10(8) hematopoietic cells prepared from the fetal livers of 8-32 week old abortuses. Five patients, who died within 15 days of fetal liver infusion, are excluded from analysis. Twenty-two of the 35 evaluable patients (62%) responded favourably. Six of the 7 patients with good response were alive after 9 to 44 months (median: m = 20); one died 106 months after fetal liver infusion due to renal lithiasis. Four of the 7 with moderate response were alive after 9 to 31 months; 3 died within 16 months. Of 8 patients with minimal response, one was lost to follow-up and the others died in 3.4 to 10 months (m = 6). Median survival of responders was 15.7 months. Bone marrow cellularity became normal in 12 patients following fetal liver infusion. In seven patients, there was a relapse; 6 regained a normal bone marrow cellularity after a second or third fetal liver infusion. These data strongly suggest a role of fetal liver infusion in inducing bone marrow recovery. Of 13 non-responders, 4 were lost to follow-up and 9 died within 20 days-4.3 months (m = 1.6). Fetal liver infusion appears to be an effective therapy in patients with severe aplastic anaemia.     

Changes in Lower Leg Anterior Compartment Pressure Before,During, and After Creatine Supplementation

OBJECTIVE: To determine if 35 days of creatine supplementation (Cr) followed by 28 days of no supplementation altered lower leg anterior compartment pressure (ACP) at rest and after exercise. DESIGN AND SETTING: Subjects were divided into 2 treatment groups: (1) high dose (0.3 g Cr.kg body mass(-1).d(-1) for 7 days followed by 0.03 g Cr.kg body mass(-1).d(-1) for 28 days), or (2) low dose (0.03 g Cr.kg body mass(-1).d(-1) for 35 days). After 35 days, supplementation was terminated, and no Cr was ingested for 28 days. SUBJECTS: Sixteen physically active, healthy, college-aged males (O(2)max = 47.6 +/- 5.1 mL.kg(-1).min(-1)). MEASUREMENTS: At baseline, 7 days and 35 days of supplementation, and 28 days postsupplementation, ACP was measured preexercise and immediately, 1, 5, 10, and 15 minutes postexercise after a treadmill run at 80% O(2)max. RESULTS: For ACP, there was no significant group-by-time interaction, but there was a significant time effect for group when the data were combined. ACP was significantly increased at preexercise, immediately postexercise, and 1, 5, and 10 minutes from baseline to 7 days. ACP remained significantly elevated from baseline at 35 days immediately postexercise and 1 minute postexercise. After 28 days of no supplementation, ACP began to return to presupplementation levels, with only the 1-minute postexercise measurement significantly elevated from baseline. CONCLUSIONS: Creatine supplementation increased ACP at rest and after exercise, and ACP began to return to normal after 28 days of no supplementation.     

Anti-L3T4 antibody treatment suppresses hepatic granuloma formation and abrogates antigen-induced interleukin-2 production in Schistosoma mansoni infection

In murine schistosomiasis mansoni, granulomatous inflammation is an immune response that involves egg antigen presentation to T cells in the context of class II major histocompatibility complex determinants and subsequent inflammatory lymphokine production by delayed-hypersensitivity (TDH) lymphocytes. In the present study, monoclonal antibodies directed against L3T4, I-A, and Lyt-2 molecules were injected intraperitoneally into S. mansoni-infected mice to study the role of these membrane antigens in the process of granuloma formation. A dramatic suppression of the hepatic granuloma size and antigen-induced interleukin-2 (IL-2) production by spleen cells was seen in mice that received anti-L3T4 monoclonal antibody treatment. The total number of cells, especially the L3T4+ T cells, was greatly diminished in the spleens. Furthermore, histopathological study of the granulomas in stained liver sections demonstrated the paucity of eosinophils and macrophages, absence of epithelioid cells and multinucleated giant cells, and minimal collagen deposition within the lesions. Damaged hepatocytes were also seen surrounding these ill-formed granulomas. In contrast, anti-I-A monoclonal antibody treatment partially suppressed IL-2 production, although granuloma size and cellular composition remained the same. Mice that received anti-Lyt-2 monoclonal antibody did not show any changes in either IL-2 production or hepatic granulomatous inflammation. The data presented in this paper indicate a crucial role for L3T4 molecules present on a subset of class II major histocompatibility complex-restricted TDH cells in IL-2 production and the generation of the granulomatous response.     

Anxiety disorders: diagnosis and treatment

Pathologic anxiety, marked by inappropriate apprehension and/or fear, causes patients to seek help. Anxiety is associated with a wide variety of physical illnesses, and these must be initially considered when making a diagnosis. Similarly, anxiety associated with a wide variety of psychiatric syndromes must also be considered. Finally, the possibility of transient situational anxiety is ever present. Once it is determined that a primary anxiety disorder exists, then the presence or absence of phobias, panic attacks, and chronic "free-floating" anxiety will fully characterize the disorder. With an accurate diagnosis in hand, a multifaceted treatment approach can be designed. Effective treatments now exist for phobic and panic disorders, and more effective treatment for chronic generalized anxiety may be forthcoming.     

Strand-Specific Reverse Transcription PCR for Detection of Replicating SARS-CoV-2

We developed an assay that detects minus-strand RNA as a surrogate for actively replicating severe acute respiratory syndrome coronavirus 2. We detected minus-strand RNA in 41 persons with coronavirus disease up to 30 days after symptom onset. This assay might inform clinical decision-making about patient infectiousness.     

Response of the ENPP1-Deficient Skeletal Phenotype to Oral Phosphate Supplementation and/or Enzyme Replacement Therapy: Comparative Studies in Humans and Mice

Inactivating mutations in human ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) may result in early-onset osteoporosis (EOOP) in haploinsufficiency and autosomal recessive hypophosphatemic rickets (ARHR2) in homozygous deficiency. ARHR2 patients are frequently treated with phosphate supplementation to ameliorate the rachitic phenotype, but elevating plasma phosphorus concentrations in ARHR2 patients may increase the risk of ectopic calcification without increasing bone mass. To assess the risks and efficacy of conventional ARHR2 therapy, we performed comprehensive evaluations of ARHR2 patients at two academic medical centers and compared their skeletal and renal phenotypes with ENPP1-deficient Enpp1^asj/asj mice on an acceleration diet containing high phosphate treated with recombinant murine Enpp1-Fc. ARHR2 patients treated with conventional therapy demonstrated improvements in rickets, but all adults and one adolescent analyzed continued to exhibit low bone mineral density (BMD). In addition, conventional therapy was associated with the development of medullary nephrocalcinosis in half of the treated patients. Similar to Enpp1^asj/asj mice on normal chow and to patients with mono- and biallelic ENPP1 mutations, 5-week-old Enpp1^asj/asj mice on the high-phosphate diet exhibited lower trabecular bone mass, reduced cortical bone mass, and greater bone fragility. Treating the Enpp1^asj/asj mice with recombinant Enpp1-Fc protein between weeks 2 and 5 normalized trabecular bone mass, normalized or improved bone biomechanical properties, and prevented the development of nephrocalcinosis and renal failure. The data suggest that conventional ARHR2 therapy does not address low BMD inherent in ENPP1 deficiency, and that ENPP1 enzyme replacement may be effective for correcting low bone mass in ARHR2 patients without increasing the risk of nephrocalcinosis. © 2021 American Society for Bone and Mineral Research (ASBMR).     

Prostate cancer presentation,treatment selection,and outcomes among men with HIV/AIDS: A clinical stage,race, and age-matched contemporary analysis

PurposeTo compare the clinical presentation, treatment receipt, and oncologic outcomes between human immunodeficiency virus-seropositive (HIV+) and seronegative (HIV?) men with prostate cancer (CaP) matched by age, clinical stage, and race.Materials and methodsA retrospective review of 3,135 men treated for CaP from 2000 to 2016 was performed. HIV+ patients (N = 46) were matched 1:2 to 3 to HIV? men (N = 137) by age, race, and clinical stage. Clinicopathologic features and primary treatment received were compared between cohorts. Associations between HIV status and progression-free, cancer-specific, and overall survival were compared by HIV status using the Kaplan-Meier method and Cox proportional hazards analysis.ResultsAfter matching, men with and without HIV were similar with respect initial prostate-specific antigen, Gleason Sum, and Eastern Cooperative Oncology Group (ECOG) performance status. Among HIV+ men, 67.4% had a history of acquired immune deficiency syndrome, and 91.3% were on highly active antiretroviral therapy at CaP diagnosis. Among men with localized disease, HIV+ men were more likely to receive radiation (59.5% vs. 44.8%) or no therapy (13.5% vs. 4.3%) and less likely to receive surgery (16.2% vs. 30.2%), or to initiate active surveillance (10.8% vs. 16.4%; P = 0.04 overall). There were no differences in rates of clinical progression, development of castration resistance, or CaP death by HIV status. However, HIV+ status was associated with inferior overall survival (hazard ratio 2.89, P = 0.04).ConclusionsWhile most HIV+ patients had a history of acquired immune deficiency syndrome; HIV was well controlled in the majority of patients at the time of CaP diagnosis. While oncologic outcomes were similar between HIV+ and HIV? men, significant differences in treatment selection were observed. Further research is necessary to understand differences in treatment election by HIV status and to define optimal CaP treatment selection in men with HIV.