Significant Macroscopic Changes Research Articles

Exploring pNIPAM lyogels: Experimental study on swelling equilibria in various organic solvents and mixtures, supported by COSMO-RS analysis

Stimuli-responsive lyogels are considered to be smart materials due to their capability of undergoing significant macroscopic changes in response to external triggers. Due to their versatile and unique properties, smart lyogels exhibit great potential in various applications such as drug delivery or actuation processes. While Poly-N-isopropylacrylamide (pNIPAM) is widely known as a thermo-responsive material, it also shows significant solvent-responsive swelling behavior. For the systems tested, polar solvents induce strong swelling due to hydrogen bonding with the amide group, nonpolar solvents lead to significant shrinkage of the lyogels. The aim of this study is to investigate and to model this behavior for future application in chemical or biochemical reactors. As a current area of research, incorporating smart lyogel technology into (bio-)chemical reactors facilitates the development of smart reactor systems. Applying thermodynamic modelling with the gE model COSMO-RS on the monomer or oligomers of pNIPAM, the correlation between solvent-polymer interactions and the degree of swelling can be observed. pNIPAM derivatives exhibit low infinite dilution activity coefficients (IDACs) in polar solvents with large degrees of swelling, while displaying an increase of IDACs in nonpolar solvents. Hydrogen bonds dominate the swelling behavior of lyogels not only in pure solvents but also in mixtures of solvents with varying polarity. Even in mixtures containing high amounts of nonpolar solvents, large degrees of swelling were observed due to the uptake of the polar solvent in the lyogel matrix. This effect can be observed in binary solvent mixtures but also in representative mixtures along an esterification reaction with varying carboxylic chain length of alcohol and carboxylic acids.

Diagnostic challenges and forensic implications in a case of infantile fatal myocarditis

We present the case of a 23-month-old child who died less than 24 h after the onset of cardiac symptoms, despite being admitted to the hospital 72 h earlier. Autopsy revealed no significant macroscopic changes, and histologic examination revealed focal lymphocytic myocarditis with myocyte disruption, diffuse alveolar damage in the exudative phase, and generalized lymphocytic immune activation in other organs. Ante-mortem and post-mortem microbiological exams did not clearly prove a causative role of infectious agents. The peculiarity of this case was characterized by the contrast between the severe clinical features and the mild cardiac histological findings. This discrepancy, coupled with the suspicion of a viral causative role based on both ante-mortem and post-mortem microbiological examinations, presented significant challenges in reaching an etiological diagnosis. This case also confirms that the diagnosis of myocarditis in children cannot be made solely on the basis of histological cut-offs or microbiological results. Using abductive reasoning, various diagnostic hypotheses were formulated and evaluated to arrive at the final diagnosis of fatal myocarditis of viral or post-viral origin. Data from post-mortem examination are often the only source of information that is available to the experts, especially in cases of sudden infant death syndrome. In such cases, the forensic pathologists should accurately evaluate findings that may appear to indicate a different etiology, and, in the absence of clinical or radiological data, interpret post-mortem data in a logically correct manner. The autopsy is the first essential step to evaluate the cause of death and must be integrated with the results of ante- and post-mortem diagnostic tests in a holistic approach, which is crucial to allow forensic pathologists to provide an appropriate and relevant opinion.

The reasons of unsatisfactory results of extracorporeal shock wave lithotripsy in patients with ureterolithiasis

The article dedicate to the problem of failure of extracorporeal shockwave lithotripsy in patients with ureterolithiasis and reveal the changes which appear in the ureter in the location of the stone.The aim. Analysis of the results of treatment in patients, suffering ureteric stones, using the ureterolithotripsy procedure after failure extracorporeal shockwave lithotripsy.
 Materials and methods. In 137 patients with ureteric stones, whom ureterolithotripsy procedure after failure extracorporeal shockwave lithotripsy was conducted, the symptoms of the disease, the diagnostic methods value, efficacy of surgical treatment and reasons of the failure of previous method of treatment were analyzed.
 Results. In 135 patients endoscopic removal of stones has been succeeded, in 2 patients because of total obliteration of the ureter, uretero-ureteral anastomosis has been performed. If the symptoms, with are characteristic of ureterolithiasis, persists up to one week stones don’t cause significant macroscopic changes to the ureter wall. If the stone persists in the ureter longer than a week we identified local appearing of oedema. Long–term (more than two months) ureteric stone persistence increase the risk of intramucosal “ingrowth” of the calculi greatly.
 Conclusion. The URS and ESWL are high effective and minimal invasive methods of surgical intervention for patients with ureterolithiasis, guaranteeing high level of postoperative “stone free rate”. Prolongation of the stone insertion time in the ureter causes the ureteric wall changes, complicating performance of minimal invasive interventions (ureterolithotripsy and extracorporeal shock–wave lithotripsy) and reduce its efficacy.

Challenge of Naïve and Vaccinated Pigs with a Vaccine-Derived Recombinant Porcine Reproductive and Respiratory Syndrome Virus 1 Strain (Horsens Strain).

In July 2019, a vaccine-derived recombinant Porcine reproductive and respiratory syndrome virus 1 strain (PRRSV-1) (Horsens strain) infected more than 40 Danish sow herds, resulting in severe losses. In the present study, the pathogenicity of the recombinant Horsens strain was assessed and compared to a reference PRRSV-1 strain using a well-characterized experimental model in young SPF pigs. Furthermore, the efficacies of three different PRRSV-1 MLV vaccines to protect pigs against challenge with the recombinant strain were assessed. Following challenge, the unvaccinated pigs challenged with the Horsens strain had significant increased viral load in serum compared to all other groups. No macroscopic changes were observed at necropsy, but tissue from the lungs and tonsils from almost all pigs were PRRSV-positive. The viral load in serum was lower in all vaccinated groups compared to the unvaccinated group challenged with the Horsens strain, and only small differences were seen among the vaccinated groups. The findings in the present study, combined with two other recent reports, indicate that this recombinant “Horsens” strain indeed is capable of inducing infection in growing pigs as well as in pregnant sows that is comparable to or even exceeding those induced by typical PRRSV-1, subtype 1 strains. However, absence of notable clinical signs and lack of significant macroscopic changes indicate that this strain is less virulent than previously characterized highly virulent PRRSV-1 strains.

Encephalic Toxoplasm in a White-Eared Possum (Didelphis albiventris)

Background: Toxoplasmosis is caused by Toxoplasma gondii, an obligate intracellular protozoan that belongs to the Aplicomplexa phylum, coccidian subclass, and affects all warm-blooded animals. The role of opossums in the epidemiology of toxoplasmosis in Brazil is not fully understood, and there are very few descriptions of toxoplasmosis lesions in these animals. This report describes the anatomopathological, molecular and immunohistochemical findings of a case of encephalic toxoplasmosis in free-living white-eared possum (Didelphis albiventris).Case: A young male opossum (D. albiventris), was treated at the Veterinary Hospital of Wild Animals of the University of Brasília, Federal District. The animal was apathetic, uncoordinated, reluctant to move, and had an exposed proximal fracture in the left radius and ulna with laceration of muscles and adjacent tendinous structures. Amputation on the left thoracic limb was performed followed by analgesia and antibiotic therapy. The environment is frequented by other wild animals, and stray cats have access to the patio of the building. Twenty-five days after arriving at the hospital, the animal was found dead in its cage. After death, a necropsy was performed. Organ fragments from the abdominal cavity, thoracic and central nervous system were collected, processed routinely for histology and stained with hematoxylin and eosin. Macroscopic lesions in the central nervous system were not observed. On microscopy, the brain showed moderate random glial nodules throughout the neuropil associated with the presence of spherical to elongated parasitic cysts of about 20 µm, with a thin wall and with its interior full of bradyzoites, consistent with Toxoplasma gondii. There was also moderate fibrinoid necrosis and moderate multifocal lymphoplasmacytic infiltrate surrounding the blood vessels (perivascular cuffs) To investigate the etiology of the brain injury, brain sections were subjected to immunohistochemistry (IHC) and real-time polymerase chain reaction (qPCR) technique for detection of T. gondii and Neospora caninum. Immunostaining for T. gondii in the cyst wall and in bradyzoites and negative immunostaining for N. caninum. qPCR was positive for T. gondii and negative for N. caninum.Discussion: Diagnosis of encephalic toxoplasmosis in a Didelphis albiventris was possible based on histopathological, immunohistochemical and molecular findings. The morphological classification of the brain lesion was important for the diagnosis. Brain toxoplasmosis in opossums usually results in focal areas of malacia on macroscopy and focally extensive necrosis on microscopy, neutrophil infiltrate, calcified necrotic material, and perivascular cuffs of lymphocytes and plasma cells. In the present case, similar histopathological lesions were noted, but no significant macroscopic changes were observed. The etiology here was defined by immunohistochemistry and qPCR, techniques proven to be useful and with good specificity for diagnosing toxoplasmosis in mammals. It is believed that the positive immunohistochemical and molecular result for Toxoplasma gondii together with the negative result for Neospora caninum were conclusive for the diagnosis. Thus, we demonstrate here a post mortem diagnosis of toxoplasmosis in a free-living synanthropic opossum and the use of anatomopathology, immunohistochemistry and real-time polymerase chain reaction as a diagnostic option for this disease in opossums. Keywords: Toxoplasma gondii, marsupial, immunohistochemistry, Real time PCR, protozoal encephalitis.Título: Toxoplasmose encefálica em um gambá-de-orelha-branca (Didelphis albiventris)Descritores: Toxoplasma gondii, marsupial, imuno-histoquímica, Real time PCR, encefalite protozoal.

The contact ureterolithotripsy in treatment of ureterolythiasis

Objective. Аnalysis of the treatment results in patients, suffering ureteric calculi, using the contact ureterolithotripsy procedure.
 Маterials and methods. In 104 patients with ureteric calculi, in whom ureteroscopy with further laser contact ureterolithotripsy was conducted, symptoms of the disease were analyzed, as well as the diagnostic methods value, peculiarities and efficacy of surgical treatment.
 Results. In all the patients endoscopic extraction of calculi have been succeeded. Calculus does not cause significant macroscopic changes in ureter, if symptoms, characteristic for ureterolithiasis, persists up to one week. Local edema is formed, if a calculus persists in ureter longer than a week. Long-term (more than two months) local ureteric persistence of calculi enhances the risk of its intramucosal intraureteric «ingrowth» greatly.
 Conclusion. The contact ureterolithotripsy constitutes a highly effective and miniinvasive method of surgical intervention in ureterolithiasis, guaranteeing high level of postoperative “stone free rate”. Prolongation of the calculi ureteric insertion time without a process of a stone discharge causes the ureteric wall changes, complicating performance of miniinvasive interventions (the contact ureterolithotripsy and a distant shock-wave lithotripsy).

Reversible Polymer-Chain Modification: Ring-Opening and Closing of Polylactone.

A reversible polymer modification involving structural changes of the polymer chains was accomplished for the copolymer of CO2 and butadiene. The bicyclic structures were opened by hydrolysis and aminolysis reactions of the lactone moiety. For the hydrolysis product, the ring-closing of the ring-opened product was achieved by simply heating without any reagents or solvents. Nuclear magnetic resonance and matrix assisted laser desorption/ionization time-of-flight analyses and size-exclusion chromatography measurement of the polymer before ring-opening and after ring-closure suggested the retention of the polymer structure as well as the molecular weight and polydispersity during the reversible processes, proving that the modification can be performed without significant macroscopic changes of the polymer structure.

Patrones de envejecimiento cerebral

Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing. The aged human brain has been described as showing weight and volume loss and increased ventricular size. However, neuroimaging shows significant variation and many healthy elderly individuals show no significant macroscopic changes. In most brain regions, the number of neurons remains stable throughout life. Neuroplasticity does not disappear with ageing, and changes in dendritic arborization and the density of spines and synapses are more closely related to brain activity than to age. At the molecular level, although the presence of altered Tau and β-amyloid proteins is used as a biomarker of neurodegenerative disease, postmortem studies show that these abnormal proteins are common in the brains of elderly people without dementia. Finally, due to the relationship between neurodegenerative diseases and metabolic alterations, this article analyses the influence of insulin-like growth factor and ageing, both in animal models and in humans, and the possible neuroprotective effect of insulin.

Rationally Designed Dynamic Protein Hydrogels with Reversibly Tunable Mechanical Properties

Protein hydrogels have attracted considerable interest due to their potential applications in biomedical engineering. Creating protein hydrogels with dynamic mechanical properties is challenging. Here, the engineering of a novel, rationally designed protein-hydrogel is reported that translates molecular level protein folding-unfolding conformational changes into macroscopic reversibly tunable mechanical properties based on a redox controlled protein folding-unfolding switch. This novel protein folding switch is constructed from a designed mutually exclusive protein. Via oxidation and reduction of an engineered disulfide bond, the protein folding switch can switch its conformation between folded and unfolded states, leading to a drastic change of protein's effective chain length and mechanical compliance. This redox-responsive protein can be readily photochemically crosslinked into solid hydrogels, in which molecular level conformational changes (folding-unfolding) can result in significant macroscopic changes in hydrogel's physical and mechanical properties due to the change of the effective chain length between two crosslinking points in the protein hydrogel network. It is found that when reduced, the hydrogel swells and is mechanically compliant; when oxidized, it swells to a less extent and becomes resilient and stiffer, exhibiting an up to fivefold increase in its Young's modulus. The changes of the mechanical and physical properties of this hydrogel are fully reversible and can be cycled using redox potential. This novel protein hydrogel with dynamic mechanical and physical properties could find numerous applications in material sciences and tissue engineering.

Mass spectrometry-based metabolite profiling in the mouse liver following exposure to ultraviolet B radiation.

Although many studies have been performed on the effects of ultraviolet (UV) radiation on the skin, only a limited number of reports have investigated these effects on non-skin tissue. This study aimed to describe the metabolite changes in the liver of hairless mice following chronic exposure to UVB radiation. We did not observe significant macroscopic changes or alterations in hepatic cholesterol and triglyceride levels in the liver of UVB-irradiated mice, compared with those for normal mice. In this study, we detected hepatic metabolite changes by UVB exposure and identified several amino acids, fatty acids, nucleosides, carbohydrates, phospholipids, lysophospholipids, and taurine-conjugated cholic acids as candidate biomarkers in response to UVB radiation in the mouse liver by using various mass spectrometry (MS)-based metabolite profiling including ultra-performance liquid chromatography-quadrupole time-of-flight (TOF)-MS, gas chromatography-TOF-MS and nanomate LTQ-MS. Glutamine exhibited the most dramatic change with a 5-fold increase in quantity. The results from altering several types of metabolites suggest that chronic UVB irradiation may impact significantly on major hepatic metabolism processes, despite the fact that the liver is not directly exposed to UVB radiation. MS-based metabolomic approach for determining regulatory hepatic metabolites following UV irradiation will provide a better understanding of the relationship between internal organs and UV light.

Síndrome diarreico y carcinoma de células renales

A 36-year-old male with diarrhea and loss of weight underwent testing for blood chemistry, TSH, immunological parameters, celiac profile, and parasites in feces. All results were normal. C-reactive protein was elevated. Colonoscopy up to the cecum was normal, and a small-bowel follow-through with barium showed no alterations. Abdominal echography showed a left renal upper-pole mass about 4 cm in diameter, round, and isoechoic with hyperechoic areas inside consistent with necrotic areas (Fig. 1). CTA confirmed this lesion as 4.3 cm in size, hypodense, confined to the kidney and not affecting the perirenal fat or vascular pedicle. The patient was sent to the Urology Department and underwent a left laparoscopic nephrectomy -a mass could be macroscopically seen in a pole, with a complete Gerota’s capsule and no significant macroscopic changes. Cuts allowed identifying a rounded, well delimited lesion 4.8 x 4.5 cm in size in that pole, with a yellowish-brownish parenchyma with small millimetric cavities that was friable at the cut close to the renal capsule. The diagnosis was of papillary renal cell carcinoma, type 2 according to Delahunt and Eble (Fig. 2). The patient is now asymptomatic, and diarrhea is no longer present after surgery.

Biocompatibility evaluation of dura mater substitutes in an animal model

Dura-Guard® Dural Repair Patch, PRECLUDE® Dura Substitute, and Codman® ETHISORB™ Dura Patch were evaluated in a six-month dural tissue reaction study in rabbits. Bilateral craniotomy was followed by subdural implantation for each dura mater substitute. The surgical procedure for the sham control group was the same except that no material was implanted. Implantation of all of these dura mater substitutes for 28, 91, or 182 days post-implantation did not result in any deaths or clinical neurobehavioral abnormalities, changes in cerebrospinal fluid, or significant macroscopic changes at necropsy. However, histomorphologic evaluation of the implantation sites revealed some differences in the tissue response to these materials. For Dura-Guard Dural Repair Patch, a nonabsorbable material derived from bovine pericardium, the implantation site was characterized by fibrosis of the overlying area with islands of osseous metaplasia and adhesions to the brain surface. Over time, infiltrative fibrosis of the implant resulted in separation of the collagenous layers of the implant and compression of the underlying brain. Fibrosis of the overlying area that incorporated this material formed a 'replacement' dura mater. Adhesions to the brain surface observed initially were still present at six months post-implantation. Implantation of PRECLUDE Dura Substitute, a nonabsorbable material comprised of expanded polytetrafluoroethylene, resulted in virtually no early reaction, and few adhesions to the brain surface at any time period. Although this material was eventually incorporated by fibrosis, islands of osseous metaplasia were also observed in this 'replacement' dura mater. The tissue reaction to Codman ETHISORB Dura Patch, an absorbable material comprised of polyglactin 910 and polydioxanone, was generally characterized by low-grade granulomatous inflammation and initial adhesions to the brain surface. The three-dimensional structure of this implant acted as a scaffold to guide the development and integration of a 'replacement' dura mater. The absorption of the material was associated with complete resolution of the inflammatory reaction, a lack of cerebral adhesions, and restoration of the normal architecture of this region. In conclusion, subdural implantation of Dura-Guard Dural Repair Patch, PRECLUDE Dura Substitute, or Codman ETHISORB Dura Patch in rabbits for up to six months resulted in the eventual restoration of the dura mater without significant adverse effects. However, osseous metaplasia associated with nonabsorbable Dura-Guard Dural Repair Patch and PRECLUDE Dura Substitute, and the infiltration of Dura-Guard Dural Repair Patch by fibrosis suggests that long-term follow-up may be needed after the use of these materials in patients. An advantage of Codman ETHISORB Dura Patch was that it was completely absorbed after guiding the restoration of the dura mater without any morphological sequelae. [Neurol Res 2001; 23: 813-820]