Cytokines and growth factors in a biologic product obtained from patients' urine as immune-modulators to treat autoimmune and allergic diseases.

At "Instituto de Alergias y Autoinmunidad Dr. Maximiliano Ruiz Castañeda, A.C." in Mexico City, a non-traditional health care center focused on the treatment of autoimmune and allergic diseases using personalized medicine, an alternative treatment referred to as an "immune-modulator" has been developed. In this study, we will refer to this treatment substance as the "immune-modulator." In brief, a urine sample is collected from the patient and processed to obtain the peptide fraction, which is conditioned and then administered sublingually to the patient. Sample processing involves multiple steps aimed at the removal of toxic compounds and enrichment for cytokines, growth factors, and other immune peptides that may contribute to the function of the immune-modulator. This treatment has been administered for many years, and patients testify that it is useful and reliable. Despite the benefits of this treatment, the molecular mechanisms underlying its effects have not been thoroughly investigated. Therefore, this study aims to identify immunoregulatory peptides, such as cytokines and growth factors, in the immune-modulator. Urine and immune-modulator concentrations of cytokines and growth factors were assessed using a Luminex assay. Twenty-one cytokines and growth factors were identified in immune-modulator samples. MCP-1 was identified in 100% of the samples; MIP-1ß, IL-8, RANTES, INF-γ, and IP-10 were identified in approximately 65-70% of samples; IL5, IL-1B, and IL-17 in 50-60%; eotaxin, VEGF, IL-6, and FGF in about 40%; MIP-1α, IL-9, GM-CSF, G-CSF, IL-12, and IL-15 in about 20-30%; and IL-13 and PDGF-bb were identified in <6% of samples. Additionally, patients exhibited significant changes in IL-1ß, IFN-γ, and MCP-1 concentrations after treatment with the immune-modulator, whereas healthy individuals showed no significant change in response to the treatment. The immune-modulator is an alternative treatment based on the administration of cytokines and growth factors obtained from the urine of patients. In this study, its composition was characterized. The isolated products could be responsible for the effects of the immune-modulator. Further trials are required to evaluate the effective delivery of these molecules by the administration route described.

Faunal mortality associated with massive beaching and decomposition of pelagic Sargassum.

In 2018, the Mexican Caribbean coast received a massive influx of pelagic Sargassum spp. that accumulated and decayed on beaches producing organic decomposition products that made the water turbid and brown. Between May and September of the same year there were several reports of mass mortality of marine biota in this area. From these reports we estimate that organisms belonging to 78 faunal species died as result of this event, with demersal neritic fish and Crustacea being the most affected groups. The cause of mortality appears to be the combined effect of high ammonium and hydrogen sulfide concentrations, together with hypoxic conditions. If massive arrival of pelagic Sargassum spp. continues and algae is left to decay on the beach in large volumes then deterioration in water quality could affect coral reefs close to shore. Furthermore, barriers placed in lagoons to intercept the Sargassum spp. before it reaches the beach could impact reef fauna if the algae is left to die and sink on site.

Orthotopic implantation of colon carcinoma cells provides an experimental model in the rat that replicates the regional spreading pattern of human colorectal cancer.

Our goal was to develop an experimental model of colon adenocarcinoma based on the orthotopic implantation of tumour cells in syngenic rats which would replicate the pattern of regional spreading of human colorectal adenocarcinoma. We used cell line DHD/K12-PROb and 62 BD-IX rats with intra-caecal injection of 1 x 10(6) cells. Macroscopic and histological examinations were made at different times after injection (from 1 to 16 weeks) with particular emphasis on caecal lesions and tumours were classified according to the TNM system (UICC, 1987). Our results suggest that this model provides a step-by-step reproduction of the development of human colorectal adenocarcinoma. It also allows us to predict how long it will take to achieve a certain degree of local spreading, which is essential for the design of cancer-related experiments. Moreover, our model has the advantage that it uses immunocompetent rats, which facilitates its application.

Establishment of an experimental model of colon cancer which replicates the regional extension pattern of human colorectal adenocarcinoma.

OBJECTIVE: The aim of this study was to develop an experimental model of colon adenocarcinoma based on the orthotopic implantation of tumor cells in syngenic rats, which reproduces the regional extension pattern of human colorectal adenocarcinoma. EXPERIMENTAL DESIGN: Cell cultures: cell line DHD/K12-PROb. ANIMALS: BD-IX rats. Tumour implantation: intra-caecal injection containing 1 x 10(6) cells in 0.25 ml of PBS. DESIGN: randomized observation study of three groups until five rats were shown to have cancer implantations in each group: GROUP I: sacrificed one week after the injection (n = 6), GROUP II: sacrificed two weeks after the injection (n = 9), GROUP III: sacrificed four weeks after the injection (n = 10). MEASUREMENTS: macroscopic and histological examination, with particular emphasis on caecal lesions. Tumours were classified according to the TNM system (UICC, 1987). RESULTS: GROUP I: tumors were found in 83% of cases (5/6), 4 of which were classified as T1N0M0 and 1 as T2N0M0. GROUP II: tumour in 55.5% of cases (5/9). One was classified as T1N0M0, 3 as T2N0M0 and 1 as T3N0MPER. GROUP III: tumors were found in 50% of cases (5/10). Two were classified as T4N0M0, 2 as T4N1MPER, and 1 as T3N1MPER. The degree of wall infiltration of the tumor showed statistical differences between groups I and III and groups II and III (p < 0.05). CONCLUSIONS: Our model offers a step by step reproduction of events described for human colorectal adenocarcinoma. It was therefore easy to predict how long it would take to achieve a degree of local extension, which is essential in the design of cancer experiments. Moreover, this model has the advantage that it uses immunocompetent rats, which facilitates the methodology.

Does neostigmine have a deleterious effect on the resistance of colonic anastomoses?

The aim of the present study was to evaluate the effects of neostigmine as a final anaesthetic manoeuvre on colonic anastomoses. A colonic anastomosis was constructed in 40 Sprague-Dawley rats. The animals were divided into two groups: (1) rats receiving intravenous saline solution (placebo); and (2) rats receiving an intravenous injection of neostigmine. The size of the caecum, and the diameters of the pre-anastomotic and post-anastomotic colon were measured during the operation and 4 days after surgery, when all the animals were sacrificed. At this time, the presence of adhesions was also investigated. Each segment containing an anastomosis was removed, and the bursting pressure and bursting wall tension were determined. Loss of caecum diameter was significantly greater in group 2 than in group 1 (P = 0.03). Dilatation and obstruction of the colon were significantly more frequent in group 1 (dilatation, P = 0.01; obstruction, P = 0.047). Also, consumption of water by group 2 was greater than that by group 1 (P = 0.049). No statistically significant differences were found between the diameters of the colon (pre- and post-anastomosis), or with respect to general adhesions and adhesions to the anastomotic line. No significant differences were found between anastomotic resistance (determined in terms of bursting pressure and bursting wall tension) in the two groups. The inclusion of neostigmine in an anaesthetic protocol under experimental setting did not reduce the resistance of colonic anastomoses and did not compromise normal healing. Moreover, obstruction caused by peristaltic weakness might be prevented by the expulsion of stool that is induced by the strong contraction of the colonic smooth muscle.