Search

Despite the progress in the management of COVID-19, effective oral antiviral agents are still lacking. In the present review, the potential beneficial effects of molnupiravir in the management of COVID-19 are discussed. A literature search in Google Scholar, Scopus, PubMed and clinicaltrials.gov for the relevant articles regarding the pharmacokinetics, pharmacodynamics and clinical trials of molnupiravir in the management of COVID-19 is conducted. Most of the preclinical studies and available clinical trials showed a favorable short-term safety profile of molnupiravir; however, given its possible genotoxic effects, further trials are required to confirm the long-term efficacy and safety of molnupiravir in patients with COVID-19.

A new prothrombin variant, with a point mutation at nucleotide 20 029 resulting in Asp 552 to Glu substitution (prothrombin numbering), has been identified in a male newborn. Plasma prothrombin level was <3%, 16% and 60% when measured by clotting, chromogenic and immunological assays respectively. The substitution did not affect the rate of prothrombin conversion to thrombin but altered thrombin activity. Amino acid 552 has been reported to be involved in the allosteric transition, which is induced by sodium binding to thrombin. This is the first known amino acid substitution at this site to result in dysprothrombinaemia.

Hepatic and biliary structures present during embryonic Carnegie stage 23 were analyzed and compared in OFA-IOPS rat and human embryos. The group of embryos was composed of 3 rat specimens-crown rump length (CRL) 16 mm, age 16 days 5 hours post coltus- and of 1 human embryo- CRL 31 mm, age 57 days PC-. The specimens were submitted to serial histological sections with graphic reconstruction. In both species, the basic architecture of liver parenchyma was established including parenchymal cords or plates alternating with hepatic sinusoids. Veinous channels were clearly defined. The intrahepatic biliary system, referred as ductal plates (DP) developed into the periportal connective tissue while the portal spaces were not yet existing. DP was recognized either as a single layered cuboidal structure or as a double layered one dilated to form mature tubular ducts. The latter layout was more frequent in the rat. Except for gallbladder which is never present in the rat, similarity and presence of the same hepatic structure in both species at the end of the embryonic period (stage 23) suggest that the rat is a good experimental model for liver development and will be useful to understand the mechanism of congenital anomalies and specially the involvement of ductal plates in the congenital diseases of intrahepatic bile ducts.

Objective: The process of aneurysm formation after laser welding is described., Summary Background Data: The mechanism of aneurysm formation after laser-assisted microarterial anastomosis is presently unclear., Methods: A series of 830-nm diode-laser-assisted longitudinal aortorrhophy with a condition of 400 to 500 J/mm2 for 1 cm length of anastomosis versus conventional manual anastomoses were performed in 90 Wistar rats. To compare this technique with normal media process, a histologic examination of aneurysm formation was conducted., Results and Conclusions: The results show that there are two important factors that cause aneurysm formation after laser-assisted anastomosis: 1) the vessel wall is damaged by laser heating; 2) proliferation of collagen fiber at the adventitia is absent during media reconstruction.

Background and Objective: Interstitial Laser Hyperthermia (ILH) has been investigated since the early 80s in the treatment of deep seated tumors. The purpose of this study was to evaluate the efficiency of diode ILH (830 nm) in a subcutaneous tumor model. STUDY DESIGN/MATERIALS AND METHOD: The antitumoral effect of diode ILH was assessed in a randomized study performed on 80 Swiss nu/nu mice. The tumor model was a subcutaneously implanted HT29 colonic carcinoma. The animals were assigned to four groups of 20 mice: Groups 1 and 3 were treated by ILH, groups 2 and 4 were not treated (control groups). Tumors were removed on day 3 in groups 1 and 2, and on day 30 in groups 3 and 4. The treatment was performed on tumors of 8 mm in diameter and a volume of 140 mm3. A laser irradiation of 360 J (power: 0.2 W; irradiation time: 1800 s) was delivered through a 300 microns optical fiber implanted in the tumor. The laser parameters insured temperatures of 46 degrees C in the central part of the tumor and 42 degrees C at the periphery. Tumor features were evaluated on day 3 and day 30., Results: Untreated tumors grew rapidly up to a mean volume of 241 mm3 on day 3 (group 2) and 2,000 mm3 on day 30 (group 4). Treated tumors regressed to a mean volume of 32 mm3 on day 3 (group 1). On day 30, 40% of the tumors had totally disappeared and 60% showed partial response with small and peripheral residual tumor of 172 mm3 on an average, as to say 11.2 times smaller than in group 4., Conclusion: ILH with a low power 830 nm diode laser is an efficient treatment of subcutaneous tumor model. Partial responses are attributed to an insufficient heating at the tumor periphery. More precise control of the peripheral tumor temperature will improve the ILH results.

A diode-laser (830 nm)-assisted carotid artery end-to-end microanastomosis (LAMA) and a contralateral manual suture anastomosis (CMA) were performed in 70 Wistar rats. The vessel sealing was performed on the left carotid by laser pulses (average 3) of 500 mW power and 4.5 sec exposure time, the beam being focused on a spot of 300 microns diameter (700 W/cm2). The CMA was achieved on the right carotid by six 10-0 stitches. From day 0 to day 210, 40 specimens underwent scanning electron microscopy. The laser impact produced a wall injury of 100 microns in width, with an immediate sealing effect due to protein denaturation and collagen fusion of media and adventitia. The anastomosis became re-endothelialized by day 3, while the longitudinal arrangement of the endothelial cells was restored from day 10 on. In the long term, a thick collagenous meshwork of collagen and elastic fibers maintained the strength of the media, while normal endothelium covered the anastomosis. Inversely, after CMA vessel repair was delayed, and the anastomotic line was more irregular and underlined by medial fibrotic scar. In both anastomoses, the patency rate was 93 percent, with nonlethal complications. The advantages of LAMA vs. CMA were: shorter operating time (13 min/22 min), reduced intraoperative trauma, better healing of endothelium, and a miniaturization of the laser source well adapted to microsurgery.

Direct diode laser carotid (0.7-1.2 mm) end-to-end microanastomosis versus contro-lateral manual suture microanastomosis (CMA) were performed in 70 Wistar rats. The laser beam-wavelength 830 nm- was transmitted through a micromanipulator and provided a focused spot of 300 microns in diameter. After placement of three 10.0 Ethilon stitches for edge coaptation, the laser anastomosis was performed using laser shots (average 3) of 500 mW power, 4.5 s duration and 700 W/cm2 irradiance each. CMA was performed by six 10.0 stitches. Good vascular flow was confirmed by macroscopic controls, Doppler spectral analysis (n = 548) and digitalized angiography (n = 18) performed from day 0 to day 210. The patency rate (93%) as well as the complication rate (5/66) were similar in both series. Nevertheless light and scanning electron microscopy (n = 82) showed the morphological superiority of laser anastomosis: reendothelialization by day 3 and medial collagen restructuration by day 10 whilst after CMA, the arterial wall repair was delayed and the medial scar occupied by fibrotic tissue. The other advantages of the laser anastomosis were, shorter operating time minimizing organ ischemia (13 min versus 22 min), and slight endothelial trauma reducing thrombogenic risk. The technical advantages of diode laser were pointed out: miniaturization, no special maintenance and decreasing price of diodes.

Liver resection is performed in 15 pigs by means of low divergent Nd YAG laser, the hepatic pedicle being clamped and not. Clamping does not modify the efficiency of laser hemostasis during resection but increases the thickness of the ischemic layer underlying the cut liver edge. The coagulation necrosis and the edematous layer are more thickened. Migration of inflammatory cells and young fibrosis present at day 3 are gaining ground until day 15. During the same period, biliary neoductules and nodules of hepatic regeneration appear. Hepatic inflow being conserved, these reactions are delayed and less intensive. The hyperthermia, the inflammatory cellular reaction and the deepness of parenchymal damages induces by pedicle clamping are suitable for antitumoral surgery. Cooling effects of hepatic inflow are better for traumatic surgery.

Experimental hepatic resections were performed with a Nd YAG laser in 32 New-Zealand rabbits. The beam was simply transmitted by a quartz fiber of 4 degrees 2 and 8 degrees in divergence for the full angle, without any focalization. Section was possible at a power output superior to 20 W requiring short cutting time. Complete hemostasis was obtained as long as the diameter of encountered vessels did not exceed 4,5 mm. Immediately after resection the parenchyma was covered by an ischemic layer varying from 2 to 8 mm. Its thickness rapidly increased to high levels whenever the power output exceeded 40 W or when hepatic pedicle was clamped. Healing process was installed at day 30. There was no hemorrhagic, biliary or septic complication. Eleven animals were alive eight months after. Histological examination revealed four layers: a first one of carbonization, a second of condensed cells, a third of edema presenting disruption of sinusoids, and a fourth one composed of progressively normal tissue. Peripherical veins presented thrombosis of their blood content and coagulative necrosis of their wall while bile canaliculi were preserved. Fibrosis appeared in the edematous layer the 10th day and was completely formed at day 30. Electron microscopic examination revealed shadowy cells embedded in the condensed layer and mitochondrial alteration in the edematous layer. The 15th day foci of cell regenerations were registered. High levels of SGOT, SGPT and LDH (fractions IV and V) were observed immediately after resection.(ABSTRACT TRUNCATED AT 250 WORDS)

The morphological effects of liver resection in 15 pigs performed with a Nd-YAG laser beam are reported. A regular cut surface was obtained and overlayed an ischemic layer which was thinnest at a 80 W power output and a short exposure time. Hemostasis was satisfying when the encountered vessels did not exceed 4,5 mm in diameter. Semi-thin and electron microscopic examination showed "ghost" cells in the layer of coagulation necrosis, shrunken hepatocytes and red blood cells in oedematous layer and "swollen" mitochondria in the deepest layer. Clamping of the hepatic pedicle - increasing local hyperthermia by suppression of cooling vascular inflow - majorated the depth of cellular alterations and the intensivity of the post-operative inflammatory reaction. Numerous biliary ductules and active hepatocytes meant parenchymal regeneration. Good healing evolution free of complications was observed after a one year's follow up.

Many round cells are found whose number may become conspicuous. These cells may originate as well from germinal as from somatic lines. Electron microscopy is the only way to distinguish the two kinds of origin. In some specimens germinal cells predominate (spermattids, plurinuclear cells), in others there are many phagocytic cells which may ingest a great number of spermatozoa and this phenomeon may stimulate an azoospermy by failure of spermatogenesis. The study of human sperm (or testicular biopsies) by electron microscopy is needed to obtain the necessary information in order to orient diagnosis, prognosis and therapy.

The endoventricular biopsies of nine patients with alcoholic congestive cardiomyopathy were studied under the light microscope and under the electron microscope. These were compared with the results of nine cases of primary congestive cardiomyopathy, at a similar clinical stage. In the absence of specific signs, the overall appearance on both light and electron microscopy is sufficiently suggestive to allow differentiation of the two forms of cardiomyopathy. Repeated biopsies revealed disappearance of the nuclear abnormalities after withdrawal of alcohol, which introduces a prognostic element.

Fifty Wistar rats were submitted to a carotid end-to-end microanastomosis by means of a Coherent 900 Argon Laser. The laser shots were of 300 mW in power output and 5 sec. in duration with an impact area of 150 microns in diameter. The anastomosis was obtained in 4 min. using on an average 19 impacts. The luminal patency was evaluated through doppler and angiography visualization regularly achieved from day 0 up to 7 months. Light, scanning electron microscopic and ultrastructural examinations revealed that, on day 0, endothelial damages never exceeded 100 microns in width in the vicinity of the anastomotic line. Collagenous denaturation was immediately observed in the media and adventitia. The fusion line became re-endothelialized from day 3 and a collagenous network was always present in the media on day 10. Furthermore a slight fibrosis of the adventitia increased the wall resistance. The patency rate was 76% complications such as disruption and aneurysm were due to the initial technical drawbacks.

Thirty six hepatic lesions (12-18 mm) of localized hyperthermia are induced in eleven pigs by means of a Nd-YAG laser. Laser shots of 80 W/10 sec. are transmitted through a stereotaxic handpiece coupled to a water cooling circulation protecting the optic fibre. The handpiece placement is performed through an ultrasound-guided trocar. The efficiency of the irradiation is visualized by immediate temperature increasing, by ultrasonographic imaging and by anatomical verifications from operating time to four months. The center of lesion initially occupied by coagulative necrosis is rapidly marginated by a gaining ground fibrosis. At long term a fibrotic network invades the scar and confirms healing free of complications. This ultrasonographically assisted technique is proposed for deep vaporisation of disseminated hepatic metastases.

Eleven hepatic resections were performed by means of a divergent Nd:YAG laser. The beam was transmitted through a fiberoptic delivery system without any handpiece. The shortest resection time and most limited ischemic damage (4 mm) were obtained with 80-W power shoots and a low divergent beam (4 degrees 2 for full angle). The hemostatic effects of the Nd:YAG controlled bleeding from veins of up to 4.5 mm in diameter, and parenchymatic oozing from the cut edge minimized blood loss. Histological examination revealed the importance of cellular deterioration in the ischemic layer, while electron microscopy showed selective destruction of cell organelles and protein denaturation. Marked elevation of hepatic serum enzymes suggests a high degree of cellular damage. Postoperative examinations confirmed an uncomplicated healing process. Finally, the use of a flexible fiberoptic enables easy surgical manipulation.

In most spermatozoa with elongated head persists an abundant complex membranous system between the post-acromial zone and the post-nuclear region. This system has a periodical structure, the apparently spherical unit of which is 120 A in diameter; it develops between the two sheaths of the nuclear envelope and seems to be continuous with the innermost one. This system can be seen in spermatids during normal spermiogenesis and in most cases it seems to be eliminated either with cytoplasmic droplet or by swelling into the nucleus. Now, a comparable but permanent structure is located all around the head of the normal spermatozoon at the height of the posterior part of the post-acrosomial sheath. This latter system is organized under plasma membrane and only visible on the ultrathin sections made with an appropriate incidence. For some authors it might contribute to maintain the integrity of the head and that of the neck of the spermatozoon and so it might be comparable to a system of septal desmosomes. For other authors periodic structures might favour adherence and fusion of spermatozoon with ovocyte during fertilisation. The particular membranous system that we describe persists often in the spermatozoon with elongated head, by its exuberance it can trouble or delay the fusion of the two gametes at the moment of fertilisation, which might explain the sterility of men bearing this anomaly.