Two Distinct Etiologies of Gastric Cancer: Infection and Autoimmunity

Gastric cancer is a leading cause of mortality worldwide. The risk of developing gastric adenocarcinoma, which comprises >90% of gastric cancers, is multifactorial, but most associated with Helicobacter pylori infection. Autoimmune gastritis is a chronic autoinflammatory syndrome where self-reactive immune cells are activated by gastric epithelial cell autoantigens. This cause of gastritis is more so associated with the development of neuroendocrine tumors. However, in both autoimmune and infection-induced gastritis, high risk metaplastic lesions develop within the gastric mucosa. This warrants concern for carcinogenesis in both inflammatory settings. There are many similarities and differences in disease progression between these two etiologies of chronic gastritis. Both diseases have an increased risk of gastric adenocarcinoma development, but each have their own unique comorbidities. Autoimmune gastritis is a primary cause of pernicious anemia, whereas chronic infection typically causes gastrointestinal ulceration. Both immune responses are driven by T cells, primarily CD4+ T cells of the IFN-γ producing, Th1 phenotype. Neutrophilic infiltrates help clear H. pylori infection, but neutrophils are not necessarily recruited in the autoimmune setting. There have also been hypotheses that infection with H. pylori initiates autoimmune gastritis, but the literature is far from definitive with evidence of infection-independent autoimmune gastric disease. Gastric cancer incidence is increasing among young women in the United States, a population at higher risk of developing autoimmune disease, and H. pylori infection rates are falling. Therefore, a better understanding of these two chronic inflammatory diseases is needed to identify their roles in initiating gastric cancer.

Lipase Assisted (S)-Ketoprofen Resolution from Commercially Available Racemic Mixture

Ketoprofen is a commercially available drug sold as a racemic mixture that belongs to the family of non-steroidal anti-inflammatory drugs known as profens. It has been demonstrated (in vitro) that (S)-ketoprofen is around 160 times more potent than its enantiomer (R)-ketoprofen, while accumulation of (R)-ketoprofen can cause serious side effects, such as dyspepsia, gastrointestinal ulceration/bleeding, pain, salt and fluid retention, and hypertension. In this work, four commercially available lipases were systematically assessed. Parameters such as conversion, enantiomeric excess, and enantioselectivity were considered. Among them, and by evaluating lipase load, temperature, solvent, and alcohol, Candida rugosa lipase exhibited the best results in terms of enantioselectivity E = 185 ((S)-enantiopreference) with esterification conversions of c = 47% (out of 50%) and enantiomeric excess of 99%. The unreacted (R)-enantiomer was recovered by liquid-liquid extraction and racemized under basic media, which was recycled as starting material. Finally, the (S)-alkyl ketoprofen ester was successfully enzymatically hydrolyzed to the desired (S)-ketoprofen with c = 98.5% and 99% ee. This work demonstrated the benefit and efficiency of using Candida rugosa lipase to kinetically resolve racemic ketoprofen by an environmentally friendly protocol and with the recycling of the undesired (R)-ketoprofen.

Analysis on the healing of gastrointestinal ulceration by using Hemospray

Healing of gastrointestinal ulcers after Hemospray application was reported in literature. The pathophysiological mechanism of action of hemostatic powders is not elucidated so far. A prospective animal model was performed to evaluate the effect of Hemospray application on the healing process of artificially induced ulcers of the upper and lower gastrointestinal tract. In 10 pigs, 20 ulcers were created in each the upper and the lower gastrointestinal tract by endoscopic mucosal resection. 50% of the pigs were immediately treated with Hemospray application, the others were not treated. Ulcer size was measured endoscopically on day 0, 2, and 7. On day 7 the ulcers were histopathological evaluated for capillary ingrowth and the thickness of the collagen layer. After 7 days the sizes of the ulcers decreased significantly (stomach: − 22.8% with Hemospray application, − 19% without Hemospray application; rectum: − 50.8% with Hemospray application, − 49.5% without Hemospray application; p = 0.005–0.037), but without significant difference between both groups. This study shows no significant effect of the hemostatic powder Hemospray on ulcer healing in the upper and lower gastrointestinal tract compared with untreated controls, neither harmful nor beneficial. However, some trends merit further trials in patients and may indicate a possible mechanism of accelerated mucosal healing.

Flow-Directed Catheters in Hepatic Embolization Therapy—A Review with Clinical Cases

Transarterial embolization with chemotherapy and radiation is well-documented forms of treatment for liver cancers but reflux of embolic particles to nontarget tissues can result in unintended consequences such as gastrointestinal ulceration. Traditionally, operators have used coil embolization of hepatoenteric collaterals to prevent reflux. Antireflux microcatheters that contain expandable baskets (Surefire) or inflatable balloons have recently been developed as tools to avoid these side effects. We describe cases where antireflux catheters were used instead of coil embolization. Using antireflux catheters, we eliminated particle reflux into nontarget vessels. We also review the literature on antireflux catheters involved in preventing reflux during chemo- and radioembolization.

Lipid Formulations and Bioconjugation Strategies for Indomethacin Therapeutic Advances

Indomethacin (IND) is a drug which after successful clinical trials became available for general prescription in 1965 and from that time is one of the most widely used anti-inflammatory drug with the highest potencies in the in vitro and in vivo models. However, despite its high therapeutic efficacy in relieving the symptoms of certain arthritis and in treating gout or collagen diseases, administration of IND causes a number of adverse effects, such as gastrointestinal ulceration, frequent central nervous system disorders and renal toxicity. These obstacles significantly limit the practical applications of IND and make that 10–20% of patients discontinue its use. Therefore, during the last three decades many attempts have been made to design novel formulations of IND aimed to increase its therapeutic benefits minimizing its adverse effects. In this review we summarize pharmacological information about IND and analyze its new lipid formulations and lipid bioconjugates as well as discuss their efficacy and potential application.

Gastrointestinal ulceration in calves presented to a central Iowa veterinary referral facility: An underappreciated morbidity?

Summary and ImplicationsThe objective of this retrospective investigation is to identify the incidence of gastrointestinal ulceration as a co-morbidity in calves presenting to a referral veterinary hospital. Approximately 24% of calves presented to the hospital that died or were euthanized had evidence of gastrointestinal ulceration. Previous administration of an NSAID was significantly associated with the presence of ulcers, whereas antibiotic administration, age at presentation, gender, or breed were not. Clinicians and producers should consider the risk of ulceration in calves treated with NSAIDs, in light of antiulcer therapies.

Lukrecja – czy tylko słodka? Badania kliniczne, bezpieczeństwo stosowania, preparaty

Licorice has been used in medicine for ancient times. Licorice root contains active compounds with different activities: saponins, flavonoids, coumarins and essential oil. It shows diverse biological properties. This article presents current achievements with clinical trials and creates new possibilities to use licorice in therapy. It has been proved effectiveness of licorice preparations in infectious diseases of respiratory tract, aphthous stomatitis, in dermatoses and also in skin care. The conducted researches on licorice preparations, especially DGL, present on the pharmaceutical market, which are recommended in gastrointestinal ulceration, have not proved their anti-ulcerative effect. The results of some clinical trials may, however, raise doubts due to the small groups and sometimes the lack of randomization or standardization of the studied preparation. Due to its sweet taste, it is used as a corrigens.

New ibuprofen derivatives as H2S and NO donors as safer anti-inflammatory agents

Aim: Nonsteroidal anti-inflammatory drugs are expansively used worldwide. However, their prolonged administration is associated with serious side effects, especially gastrointestinal ulceration. Materials & methods: New ibuprofen derivatives hybridized with H2S- or NO-donating moieties were synthesized and evaluated for their anti-inflammatory activity and ulcerogenic effect. COX-1/COX-2 isozymes selectivity test for the most promising derivatives was performed. Molecular docking studies were performed. Results: Most of the compounds showed promising anti-inflammatory activity comparable to that of ibuprofen (% edema inhibition = 76.6 and ulcer index = 21.26) with much better gastrointestinal tract tolerance (ulcer indices ranging from 0 to 14.67), especially compound 2 -H2S donor- (% edema inhibition = 75.5 and ulcer index = 11.75) and compound 16 -NO donor- (% edema inhibition = 65.4 and ulcer index = 8.66).

Concentration-dependent Toxicity after Subcutaneous Administration of Meloxicam to C57BL/6N Mice (Mus musculus)

Studies using the Mouse Grimace Scale have shown that for many NSAID, including meloxicam, minimal doses of at least 20 mg/kg may be necessary to achieve adequate peri- and post-operative analgesia in mice. However, more data are needed to determine whether such NSAID doses exceed the threshold for gastrointestinal ulceration or induce other relevant pathology. We administered equal volumes of saline or injectable meloxicam (1 or 5 mg/mL) at a dose of 20 mg/kg SC to 20 young adult male and female C57BL/6N mice daily for 6 d and performed necropsies on all mice on the seventh day. Mice given 5 mg/mL meloxicam subcutaneously developed significantly more severe pathology at the injection site than saline controls. Pathology was characterized by full-thickness epidermal necrosis; cavitary lesions within subcutis, muscle, or fat; steatitis; and myositis. Mice that received 1 mg/mL meloxicam subcutaneously developed lesions that were qualitatively similar but far less severe than those after 5 mg/mL. However, no pathologic lesions typically associated with NSAID toxicity, such as gastric ulceration and liver and kidney lesions, were seen. These results demonstrate that although meloxicam injected subcutaneously causes concentration-dependent skin pathology at the injection site, a dose of 20 mg/kg can be safely administered subcutaneously at a concentration of 1 mg/mL for as long as 6 d.

5-Fluorouracil toxicosis in cats and dogs

5-Fluorouracil is an antineoplastic drug with a narrow therapeutic window. Pets are commonly exposed to the cream used for pre-malignant and malignant skin lesions in humans. 5-Fluorouracil poisoning is characterised by severe gastrointestinal (vomiting; diarrhoea; and gastrointestinal ulceration and haemorrhage) and neurological effects (ataxia, tremors and convulsions), and from 4–7 days bone marrow depression. Progression of signs can be rapid and control of neurological effects can be refractory to treatment. There is no specific antidote suitable for companion animals with 5-fluorouracil toxicosis, and aggressive supportive management is required. Filgrastim (a human granulocyte colony stimulating factor) can be used in the management of severe bone marrow depression, but prognosis is generally poor in dogs and cats with pronounced signs from 5-fluorouracil poisoning.