Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats.

Recently, the stable gastric pentadecapeptide BPC 157 was shown to counteract major vessel occlusion syndromes, i.e., peripheral and/or central occlusion, while activating particular collateral pathways. We induced abdominal compartment syndrome (intra-abdominal pressure in thiopental-anesthetized rats at 25 mmHg (60 min), 30 mmHg (30 min), 40 mmHg (30 min), and 50 mmHg (15 min) and in esketamine-anesthetized rats (25 mmHg for 120 min)) as a model of multiple occlusion syndrome. By improving the function of the venous system with BPC 157, we reversed the chain of harmful events. Rats with intra-abdominal hypertension (grade III, grade IV) received BPC 157 (10 µg or 10 ng/kg sc) or saline (5 ml) after 10 min. BPC 157 administration recovered the azygos vein via the inferior-superior caval vein rescue pathway. Additionally, intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were reduced, as were the grossly congested stomach and major hemorrhagic lesions, brain swelling, venous and arterial thrombosis, congested inferior caval and superior mesenteric veins, and collapsed azygos vein; thus, the failed collateral pathway was fully recovered. Severe ECG disturbances (i.e., severe bradycardia and ST-elevation until asystole) were also reversed. Microscopically, transmural hyperemia of the gastrointestinal tract, intestinal mucosa villi reduction, crypt reduction with focal denudation of superficial epithelia, and large bowel dilatation were all inhibited. In the liver, BPC 157 reduced congestion and severe sinusoid enlargement. In the lung, a normal presentation was observed, with no alveolar membrane focal thickening and no lung congestion or edema, and severe intra-alveolar hemorrhage was absent. Moreover, severe heart congestion, subendocardial infarction, renal hemorrhage, brain edema, hemorrhage, and neural damage were prevented. In conclusion, BPC 157 cured primary abdominal compartment syndrome.

A low grade osteosarcoma of the colon.

BACKGROUND: Soft-tissue osteosarcomas are very rare. Only three cases of extraskeletal osteosarcoma have been reported arising in colon and we report the first well differentiated one. PATIENTS AND METHODS: A 58-year-old woman was admitted to our hospital with a history of pain and swelling in lower right abdomen for the last 3 months. Routine laboratory tests and tumor markers (CEA, CA19-9, AFP) were all normal, as well as colonoscopy. CT-scan revealed large partly calcificated mass connected to the ascending colon without significant imbibition of contrast. Because of the size of the tumor, open surgery was indicated. An exploratory laparotomy followed by right hemicolectomy with anastomosis was performed according to oncological principles. RESULTS: Surgery and pathology confirmed the presence of 13 cm large soft tissue tumor connected to the colon by vascular pedicle. Histopathology showed spindle cells with minimal cellular atypia and focal osteoid production which lead to diagnosis of low grade osteosarcoma. Immunohistochemicaly, neoplastic cells were positive for alpha smooth muscle actin, caldesmon and desmin, but are negative for S100, CD34, CD117, DOG1, BCL-2, epithelial membrane antigen, and beta-catenin. CONCLUSION: Postoperative course went uneventful and adjuvant chemotherapy was not recommended. At 6-months follow-up there was no sign of recurrent tumor.

Corrigendum: Stable Gastric Pentadecapeptide BPC 157 Therapy for Primary Abdominal Compartment Syndrome in Rats.

[This corrects the article DOI: 10.3389/fphar.2021.718147.].

The use of piezoelectric effect to improve instrument quality and patient safety in laparoscopic surgery.

The piezoelectric properties of some natural crystals and polymers can also be used in surgery. For this purpose, a prototype of an endoscopic instrument was constructed with piezoelectric material attached to its working end with the aim of recognizing pulsating blood vessels during laparoscopic surgery. To test the properties of the new instrument in laboratory conditions, simulated blood circulation was used with the possibility of changing pressure and frequency. The instrument was tested in the pressure range of 40-180 mm Hg at constant frequency of 72/min and frequency range of 36-130 beats per minute at constant pressure of 120 mm Hg. Test results showed that the instrument with certainty recognized a pulsating "blood vessel" in the expected pressure ranges and at different blood pump frequencies. Given the piezoelectric material's very small dimensions and flexible form, it can be installed at the working end of most standard laparoscopic instruments and thus significantly increase certainty in the recognition of arteries during surgery, which would reduce the possibility of their injury or accidental ligation.

Comparison of antitumor effects of native and recombinant human interferon-α on non-small cell lung cancer cells.

BACKGROUND: In the present work, we compared the antitumor effects of native human interferon-α (IFN-α) (nHuIFN-α) and recombinant human IFN-α (rHuIFN-α) on human lung adenocarcinoma A549 cells. MATERIALS AND METHODS: The antitumor activity was determined by measuring cell viability and apoptosis, while the abundance of mRNA, measured by polymerase chain reaction (PCR), determined the potential role of p21 and survivin in antitumor activity of nHuIFN-α. RESULTS: The results show that nHuIFN-α significantly reduced A549 cell viability, compared to rHuIFN-α. The most potent effect of nHuIFN-α was also observed when apoptosis was measured. A549 cells treated with nHuIFN-α expressed a significantly higher amount of p21 mRNA, while the amount of survivin mRNA was significantly reduced. CONCLUSION: Considering both the anti-proliferative and anti-apoptotic effects of each IFN-α, we conclude that further elucidation of the mechanisms of the antitumor activity of nHuIFN-α will help in producing more effective and less toxic therapeutic protocols and preparations.

The role of interleukin-1beta and platelet-derived growth factor-AB in antifibrosis mediated by native human interferon alpha.

BACKGROUND: Commercial preparations of native human interferon alpha (nHuIFN-alpha) contain several subtypes of interferon-alpha (IFN-alpha) and traces of other cytokines. Recently, we described its antifibrotic potential and showed nHuIFN-alpha to have a greater effect than that of recombinant human IFN-alpha (rHuIFN-alpha). We hypothesized that cooperation between different cytokines in the nHuIFN-alpha preparation is essential for this effect. Considerable concentrations of interleukin-1beta (IL-1beta) and platelet-derived growth factor AB (PDGF-AB) are present in the nHuIFN-alpha preparations. METHODS: We tested the viability and the expression of procollagen type I messenger RNA (mRNA) in MRC5 fibroblasts treated with interleukin-1 beta (IL-1beta) and/or PDGF-AB, or the corresponding antibodies in combination with rHuIFN-alpha or nHuIFN-alpha. RESULTS: We showed that neither IL-1beta nor PDGF-AB significantly affect the viability of MRC5 cells. Furthermore, cell viability was not affected when IL-1beta or PDGF-AB were applied along with rHuIFN-alpha, relative to the viability of cells treated with rHuIFN-alpha only. In contrast, both cytokines suppressed the synthesis of procollagen type I mRNA. When coadministered with rHuIFN-alpha, IL-1beta enhanced the suppression induced by rHuIFN-alpha. Conversely, PDGF-AB acted as an antagonist of rHuIFN-alpha and restored partially the synthesis of procollagen type I mRNA. Interestingly, the addition of IL-1beta to the PDGF-AB/rHuIFN-alpha mix not only abolished the antagonistic activity of PDGF-AB but also decreased the synthesis of procollagen type I mRNA beyond the level achieved by IL-1beta/rHuIFN-alpha. Therefore, IL-1beta was able to reverse the activity of PDGF-AB. CONCLUSION: Our study suggests that IL-1beta is an important component of nHuIFN-alpha preparations, acting directly and indirectly to modulate the action of other components. This study provides insight into these complex cytokine networks, which is necessary for better and safer antifibrotic therapy.

Native human IFN-alpha is a more potent suppressor of HDF response to profibrotic stimuli than recombinant human IFN-alpha.

Interferon-alpha(IFN-alpha) inhibits fibroblast proliferation, differentiation into myofibroblasts, and extracellular matrix synthesis, which are key events during both normal wound repair and fibrotic lesion formation. Unlike recombinant human IFN-alpha (rHuIFN-alpha), a native human IFN-alpha (nHuIFN-alpha) consists of several IFN-alpha subtypes and traces of other cytokines produced by the Sendai virus-stimulated human leukocytes. This study compares the antifibrotic effect of nHuIFN-alpha and rHuIFN-alpha in normal human dermal fibroblasts (HDFs). Treatment of HDF culture with nHuIFNA-alpha markedly affects HDF viability, whereas different rHuIFN-alpha subtypes show various effects. Two of twelve rHuIFN-alpha subtypes (IFN-alpha B2 and IFN-alpha K) significantly reduce cell viability of HDFs compared with nontreated HDFs. However, nHuIFN-alpha significantly reduces HDF cell viability in comparison to both nontreated cells and cells treated with rHuIFN-alpha. The 50% inhibitory concentration (IC(50)) varied 10-fold between nHuIFN-alpha and rHuIFN-alpha (1,103 IU/mL and 10,762 IU/mL, respectively). The impact on procollagen type I mRNA synthesis level is comparable at low doses of IFN (100 and 500 IU/mL), whereas at the dose of 1,000 IU/mL, nHuIFN-alpha shows higher repression of collagen type I gene than does rHuIFN-alpha. Both, nHuIFN-alpha and rHuIFN-alpha antagonize the effect of exogenous transforming growth factor-beta (TGF-beta) and interleukin-4 (IL-4) as measured by the alpha-smooth muscle actin (alpha -SMA) and procollagen type I mRNA level, but the effect of nHuIFN-alpha is more pronounced. This study suggests that nHuIFN-alpha is a more potent suppressor of the HDF response to profibrotic stimuli than rHuIFN-alpha, probably because of the synergism between different IFN-alpha subtypes and antifibrotic cytokines and factors.