A Review on Lipid-Based Nanoformulations for Targeting Brain through Non-invasive Nasal Route.

The nasal method for administering nanoformulations to the brain has been examined and proven successful by prior investigators. For the treatment of central nervous system (CNS) disorders such as neuropsychiatric, depression, Alzheimer and anxiety, intranasal administration has become more popular for delivering drugs to the brain. This method offers direct transport through neuronal pathways. The lipid-based nanocarriers like nanostructured lipid carriers (NLC) appear more favorable than other nanosystems for brain administration. The nanostructured lipid carriers (NLC) system can quickly transform into a gelling system to facilitate easy administration into the nasal passages. The various compatibility studies showed that the other lipid structured-based formulations may not work well for various reasons, including a low drug filing capacity; during storage, the formulation showed changes in the solid lipid structures, which gives a chance of medication ejection. Formulations containing NLC can minimize these problems by improving drug solubility and permeation rate by incorporating a ratio of liquid lipids with solid lipids, resulting in improved stability during storage and drug bioavailability because of the higher drug loading capacity. This review aimed to find and emphasize research on lipid-based nanocarrier formulations that have advanced the treatment of central nervous system illnesses using nasal passages to reach the targeted area's drug molecules.

Biogenic synthesis of dopamine/carboxymethyl cellulose/TiO2 nanoparticles using Psidium guajava leaf extract with enhanced antimicrobial and anticancer activities.

The green synthesis of metal oxide nanoparticles (NPs) has garnered considerable attention from researchers due to its utilization of eco-friendly solvents during synthesis and cost-effective approaches. This study focuses on the synthesis of titanium oxide (TiO2) and dopamine (DA) carboxymethyl cellulose (CMC)-doped TiO2 (DA/CMC/TiO2) NP using Psidium guajava leaf extract, while also investigating the structural, optical, and morphological and biocidal potential of the prepared NPs. Significantly larger zones of inhibition were observed for DA/CMC/TiO2 NPs compared to TiO2 against various pathogens. Moreover, the MTT assay was carried out to evaluate the anticancer activity of the prepared samples against MG-63 cells, and the results revealed that DA/CMC/TiO2 NPs exhibited significantly higher level of anticancer activity compared to TiO2. The experimental results demonstrated that DA/CMC/TiO2 NPs exhibited enhanced anticancer activity in a dose-dependent manner when compared to TiO2 NPs.

A critical review on the role of nanotheranostics mediated approaches for targeting ß amyloid in Alzheimer's.

Alzheimer's is one of the most common neurodegenerative illnesses that affect brain cellular function. In this disease, the neurons in the brain are considered to be decaying steadily but consistently by the accumulation of amyloid mass, particularly the ß-amyloids, amyloid proteins, and Tau proteins. The most responsible amyloid-proteins are amyloid-40 and amyloid-42, which have a high probability of accumulating in excess over the brain cell, interfering with normal brain cell function and triggering brain cell death. The advancement of pharmaceutical sciences leads to the development of Nanotheranostics technology, which may be used to diagnose and treat Alzheimer's. They are the colloidal nanoparticles functionalised with the therapeutic moiety as well as a diagnostic moiety. This article discusses the prognosis of Alzheimer's, various nanotheranostics approaches (nanoparticles, quantum dots, aptamers, dendrimers, etc), and their recent advancement in managing Alzheimer's. Also, various in-vitro and in-vivo diagnostic methodologies were discussed with respect to nanotheranostics.

Describing the pathophysiology of Alzheimer's with respect to amyloid ß in the prognosis of the diseasePresenting the various nanotheranostics techniques for the detection and treatment of Alzheimer's diseaseNanoparticles, Aptamers, and Dendrimers used as diagnostic and treatment entitiesIn-vivo (MRI, OI) and In-vitro (STM, TRPS) diagnostic approaches for detecting Alzheimer's disease.

Odevixibat: A Review of a Bioactive Compound for the Treatment of Pruritus Approved by the FDA.

Odevixibat is synthesized through chemical modification of Benzothiazepine's structure. It is a tiny chemical that inhibits the ileal bile acid transporter and is used to treat a variety of cholestatic illnesses, including progressive familial intrahepatic cholestasis (PFIC). For cholestatic pruritus and liver disease development, bile acid transporter inhibition is a unique treatment strategy. Odevixibat reduces enteric bile acid reuptake. Oral odevixibat was also studied in children with cholestatic liver disease. Odevixibat received its first approval in the European Union (EU) in July 2021 for the treatment of PFIC in patients aged 6 months, followed by approval in the USA in August 2021 for the treatment of pruritus in PFIC patients aged 3 months. Bile acids in the distal ileum can be reabsorbed by the ileal sodium/bile acid cotransporter, a transport glycoprotein. Odevixibat is a sodium/bile acid co-transporter reversible inhibitor. An average 3 mg once-daily dose of odevixibat for a week resulted in a 56% reduction in the area under the curve of bile acid. A daily dose of 1.5 mg resulted in a 43% decrease in the area under the curve for bile acid. Odevixibat is also being evaluated in many countries for the treatment of other cholestatic illnesses, including Alagille syndrome and biliary atresia. This article reviews the updated information on odevixibat with respect to its clinical pharmacology, mechanism of action, pharmacokinetics, pharmacodynamics, metabolism, drug-drug interactions, pre-clinical studies, and clinical trials.

Prevalence of hepatopancreatic injury and clinical outcomes in patients with COVID-19 in USA.

BACKGROUND: (1) To determine the prevalence of hepatopancreatic injury in coronavirus disease 2019 (COVID-19) patients. (2) To correlate hepatopancreatic injury in COVID-19 with mortality, disease severity, and length of stay in this cohort. RESULTS: Forty-five thousand three hundred sixty patients were included in the analysis, 62.82% of which had either hepatic or pancreatic injury. There was a significant upward trend in transaminases, alkaline phosphatase, prothrombin time, bilirubin, lactate dehydrogenase, and lipase and a downward trend in albumin with an increase in disease severity. COVID-19-positive patients with hepato-pancreatic injury have a significantly higher mortality (OR 3.39, 95%CI 3.15-3.65) after controlling for the differences in age, sex, race/ethnicity, liver cirrhosis, and medication exposures. They also have increased disease severity (OR 2.7, 95%CI 2.5-2.9 critical vs mild/moderate; OR 1.4, 95% CI 1.3-1.5 severe vs mild/moderate) and longer hospital length of stay (2 days). CONCLUSION: COVID-19 can cause liver injury. Mortality, disease severity, and hospital length of stay are increased in COVID-19 patients with hepatopancreatic injury.

Endotracheal Tube Fastening Device-Related Facial Pressure Ulcers.

Acute respiratory distress syndrome (ARDS) can be present in a substantial number of hospitalized Coronavirus disease 2019 (COVID19) disease patients. Some of these patients progress to severe ARDS and require mechanical ventilation. Patients requiring mechanical ventilation and intensive care unit (ICU) admission are at an increased risk of developing pressure ulcers from multiple medical devices used in their care. In this report, we describe a case of facial pressure ulcers in a 59-year-old COVID19 positive female with ARDS requiring endotracheal intubation and mechanical ventilation.

Renin-Angiotensin-Aldosterone System Blockers Prior to Hospitalization and Their Association With Clinical Outcomes in Coronavirus Disease 2019 (COVID-19).

OBJECTIVE: To determine the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) use prior to hospitalization on clinical outcomes in coronavirus disease 2019 (COVID-19) patients. DESIGN: An observational retrospective cohort study from 178 hospitals from a large health system across the United States.  Patient population: Hospitalized patients (n=2726) with confirmed COVID-19 between January 1, 2020, and April 1, 2020. Main outcome(s) and measure(s): Outcomes during hospitalization, including disease severity by level of care, intensive care unit (ICU) admission, mechanical ventilator (MV) use, hospital length of stay, and in-hospital death. Patient demographics and comorbidities were also recorded. RESULTS: A total of 2,726 patients were included in the analysis. Three hundred ninety-eight (14.6%) patients were taking an ACEI, while 352 (12.9%) patients were taking an ARB prior to hospitalization. After adjusting for comorbidities, age, renal function, and severity of illness based on level of care, ACEI prior to admission was independently associated with decreased need for MV (odds ratio [OR] 0.56, p value 0.003) and mortality (OR 0.45, p value <0.001). Similarly, patients who took ARBs were less likely to require MV when compared to the non-renin-angiotensin-aldosterone system blockade (RAASb) group (7.4% vs 12.2%, p value 0.009, respectively). ARB prior to admission was also independently associated with decreased need for MV (OR 0.46, p value 0.001) and mortality (OR 0.66, p value 0.017) compared to the non-RAASb group. CONCLUSION: Taking ACEIs and ARBs prior to admission for COVID-19 was independently associated with decreased need for mechanical ventilation and in-hospital mortality.

Complextation of Oppositely Charged Polymer: Novel Approaches for Drug Delivery.

The polyelectrolyte complexes (PECs) are adaptable constructs shaped by electrostatic interaction between biopolymers with inverse charges. Polyelectrolyte edifices comprise an exceptional class of polymeric mixtures comprising of polyions with inverse charges, which can be charged either cationically or anionically. Significant advancement has been made in the course of recent years towards new medication conveyance frameworks. The subject of broad, essential and applied exploration covers the marvel of interpolymer collaborations and polyelectrolyte complex development. Basically, applied polyelectrolytes raise on the grounds that the advantages of supportability are perceived in the scholarly world and modern examination settings. Polyelectrolytes are a form of polymer that has endless ionizable practical arrangements. Ionized polyelectrolytes in the arrangement can form a complex with an oppositely charged particle called a polyelectrolyte complex. The review article emphasizes on PECs and their classification, characterization, as well as a critical analysis of the current research and applicability in the drug delivery technology.

Abdominal Physical Signs and Medical Eponyms: Part I. Percussion, 1871-1900.

BACKGROUND: Percussion is derived from the Latin word to hear and to touch. Percussion of the abdomen is used to detect areas of tenderness, dullness within an area of tenderness suggestive of a mass, shifting dullness representing fluid or blood, splenic, hepatic and bladder enlargement, and free air in the peritoneum. Covered are abdominal signs of percussion attributed as medical eponyms from the time-period beginning in the mid-late nineteenth century. Described is historical information behind the sign, descriptions of the sign, and implication in modern clinical practice. DATA SOURCES: PubMed, Medline, online Internet word searches, textbooks, and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: Percussion signs defined as medical eponyms were important discoveries adopted by physicians prior to the advent of radiographs and other imaging and diagnostic techniques. The signs perfected during this time-period provided important clinical cues as to the presence of air within the peritoneum or rupture of the spleen.

Abdominal Physical Signs and Medical Eponyms: Part II. Percussion and Auscultation, 1924-1980.

BACKGROUND: Percussion and auscultation are derived from the Latin words to touch and hear, respectively. Covered are abdominal percussion signs and ausculatory signs discovered from 1924 to 1980. Signs ascribed as medical eponyms pay homage to these physicians who provided new and unique insights into disease. DATA SOURCES: PubMed, Medline, online Internet word searches, textbooks, and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: Many of these signs have been discarded because of modern imaging and diagnostic techniques. When combined with a high clinical suspicion, positive results using percussion combined with palpation is a useful bedside technique in detecting splenic enlargement. Thus, some of these maneuvers remain important bedside techniques that skilled practitioners should master, and along with a meaningful history, provide relevant information to diagnosis. It is through learning about these signs that we gain a sense of humility on the difficulty physicians faced prior to the advent of techniques that now allow us an easier way to visualize and diagnose the underlying disease processes.

Abdominal Physical Signs of Inspection and Medical Eponyms.

BACKGROUND: An eponym in clinical medicine is an honorific term ascribed to a person(s) who may have initially discovered or described a device, procedure, anatomical part, treatment, disease, symptom, syndrome, or sign found on physical examination. Signs, although often lacking sufficient sensitivity and specificity, assist in some cases to differentiate and diagnose disease. With the advent of advanced technological tools in radiological imaging and diagnostic testing, the importance of inspection, the initial steps taught during the physical examination, is often overlooked or given only cursory attention. Nevertheless, in the era of evidence-based and cost-effective medicine, it becomes compelling, and we contend that a meticulously performed history and physical examination, applying the basic tenets of inspection, remains paramount prior to obtaining appropriate diagnostic tests. DATA SOURCES: PubMed, Medline, online Internet word searches and bibliographies from source text and textbooks. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSIONS: We describe the historical aspect, clinical application, and performance of medical eponymous signs of inspection found on physical examination during the 18th to 20th centuries.

Abdominal Physical Signs and Medical Eponyms: Part III. Physical Examination of Palpation, 1926-1976.

BACKGROUND: This paper describes medical eponyms associated with abdominal palpation from the period 1926-1976. Despite opposition by some, eponyms are a long standing tradition and widely used in medicine. The techniques may still be useful in some cases, assisting in the selection of an appropriate and cost-effective approach to patient care. In this piece, we cover signs named in honor of physicians who contributed to medicine by developing new palpatory techniques in an attempt to better diagnose disease of the abdominal wall, umbilicus, gallbladder, pancreas, and appendix. DATA SOURCES: PubMed, Medline, online Internet word searches, textbooks, and references from other source texts. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: We describe brief historical background information about the physician who reported the sign, original description of the sign, and its clinical application and implication into today's medical practice.

Abdominal Physical Signs and Medical Eponyms: Part II. Physical Examination of Palpation, 1907-1926.

BACKGROUND: Abdominal palpation is an important clinical skill used by physicians to detect the cause of the underlying disease. Abdominal physical signs reported as medical eponyms are sometimes helpful in supporting or confirming clinical suspicion of a diagnosis. With the advent of advanced and rapid imaging techniques physicians often know the diagnosis prior to setting their hands on patients. Nevertheless, knowledge of these signs may still remain important in settings where imaging may not be readily available and importantly provide deeper insights into the mechanism of disease. In this paper, described are medical eponyms associated with abdominal palpation from the period 1907-1926. DATA SOURCES: PubMed, Medline, on-line Internet word searches, textbooks, and references from other source text were used as the data source. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: We describe brief historical background information about the physician who reported the sign, original description of the sign, and its clinical application and implication into today's medical practice.

Effect of hydrophilic and hydrophobic polymers on permeation of S-amlodipine besylate through intercalated polymeric transdermal matrix: 3(2) designing, optimization and characterization.

OBJECTIVE: Innovation in material science has made it possible to fabricate a pharmaceutical material of modifiable characteristics and utility, in delivering therapeutics at a sustained/controlled rate. The objective of this study is to design and optimize the controlled release transdermal films of S-Amlodipine besylate by intercalating hydrophilic and hydrophobic polymers. METHODS: 3(2) factorial design and response surface methodology was utilized to prepare formulations by intercalating the varied concentration of polymers(A) and penetration enhancer(B) in solvent. The effect of these independent factors on drug release and flux was investigated to substantiate the ex-vivo, stability and histological findings of the study. RESULTS: FTIR, DSC revealed the compatibility of drug with polymers; however, the semicrystallinity in drug was observed under PXRD. SEM micrographs showed homogeneous dispersion and entanglement of drug throughout the matrix. Results from the permeation study suggested the significant effect of factors on the ex vivo permeation of drug. It was observed that drug release was found to be increased with an increase in hydrophilic polymer concentration and PE. The formulations having polymers (EC:PVPK-30) at 7:3 showed maximum drug release with highest flux (102.60 ± 1.12 µg/cm2/h) and permeability coefficient (32.78 ± 1.38 cm/h). Significant effect of PE on lipid and protein framework of the skin was also observed which is responsible for increased permeation. The optimized formulation was found to be stable and showed no-sign of localized reactions, indicating safety and compatibility with the skin. CONCLUSION: Thus, results indicated that the prepared intercalated transdermal matrix can be a promising nonoral carrier to deliver effective amounts of drug.

Abdominal Physical Signs and Medical Eponyms: Movements and Compression.

BACKGROUND: Prior to the advent of modern imaging techniques, maneuvers were performed as part of the physical examination to further assess pathological findings or an acute abdomen and to further improve clinicians' diagnostic acumen to identify the site and cause of disease. Maneuvers such as changing the position of the patient, extremity, or displacing through pressure a particular organ or structure from its original position are typically used to exacerbate or elicit pain. Some of these techniques, also referred to as special tests, are ascribed as medical eponym signs. DATA SOURCES: PubMed, Medline, online Internet word searches, textbooks and references from other source text. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: These active and passive maneuvers of the abdomen, reported as medical signs, have variable performance in medical practice. The lack of diagnostic accuracy may be attributed to confounders such as the position of the organ, modification of the original technique, or lack of performance of the maneuver as originally intended.

Minimal Change Disease Associated with High-dose Aspirin.

Minimal change disease (MCD) is an etiology of nephrotic syndrome that is more common in the pediatric population as compared to the adult population. Steroids are an effective treatment for MCD. Non-steroidal anti-inflammatory drugs (NSAIDS) are well known for their nephrotoxicity when used chronically. However, there are only few cases of NSAIDS-induced MCD that have been reported in the literature. Our patient is a 72-year-old male with no significant past medical history who presented with shortness of breath, fatigue, and malaise for few weeks. His renal function was declining in the hospital despite renal protective therapies. His medication history was significant for chronic BC powder (high dose aspirin with caffeine) use. Renal biopsy was performed and showed MCD and acute tubular necrosis. Steroids were initiated and patient's kidney function improved.

Abdominal Physical Signs and Medical Eponyms: Physical Examination of Palpation Part 1, 1876-1907.

BACKGROUND: Abdominal palpation is a difficult skill to master in the physical examination. It is through the tactile sensation of touch that abdominal tenderness is detected and expressed through pain. Its findings can be used to detect peritonitis and other acute and subtle abnormalities of the abdomen. Some techniques, recognized as signs or medical eponyms, assist clinicians in detecting disease and differentiating other conditions based on location and response to palpation. Described in this paper are medical eponyms associated with abdominal palpation from the period 1876 to 1907. DATA SOURCES: PubMed, Medline, on-line Internet word searches, textbooks and references from other source text were used as the data source. PubMed was searched using the Medical Subject Heading (MeSH) of the name of the eponyms and text words associated with the sign. CONCLUSION: We present brief historical background information about the physician who reported the sign, original description of the sign, and its clinical application and implication in today's medical practice.

Rhabdomyolysis: A Rare Adverse Effect of Levetiracetam.

Levetiracetam is an anti-epileptic that works at the synapse and binds synapse vesicle protein 2A, thereby controlling the release of neurotransmitters. Its side effects mainly include somnolence, headache, fatigue, dizziness, vomiting, and behavioral alterations. Rhabdomyolysis is a rare adverse effect of levetiracetam. The underlying pathophysiology of this adverse effect is unknown. Our patient is a 42-year-old male who was brought to the hospital with a complaint of generalized tonic-clonic seizures and urinary incontinence. His symptoms were caused by hyponatremia. Levetiracetam was started for seizure prevention along with management for hyponatremia. His creatine phosphokinase levels increased on the third day of admission to 30,000 U/L. Four days after the discontinuation of levetiracetam and with the institution of supportive therapy, the patient's rhabdomyolysis resolved.

Flushing Disorders Associated with Gastrointestinal Symptoms: Part 1, Neuroendocrine Tumors, Mast Cell Disorders and Hyperbasophila.

Flushing is the subjective sensation of warmth accompanied by visible cutaneous erythema occurring throughout the body with a predilection for the face, neck, pinnae, and upper trunk where the skin is thinnest and cutaneous vessels are superficially located and in greatest numbers. Flushing can be present in either a wet or dry form depending upon whether neural-mediated mechanisms are involved. Activation of the sympathetic nervous system results in wet flushing, accompanied by diaphoresis, due to concomitant stimulation of eccrine sweat glands. Wet flushing is caused by certain medications, panic disorder and paroxysmal extreme pain disorder (PEPD). Vasodilator mediated flushing due to the formation and release of a variety of biogenic amines, neuropeptides and phospholipid mediators such as histamine, serotonin and prostaglandins, respectively, typically presents as dry flushing where sweating is characteristically absent. Flushing occurring with neuroendocrine tumors accompanied by gastrointestinal symptoms is generally of the dry flushing variant, which may be an important clinical clue to the differential diagnosis. A number of primary diseases of the gastrointestinal tract cause flushing, and conversely extra-intestinal conditions are associated with flushing and gastrointestinal symptoms. Gastrointestinal findings vary and include one or more of the following non-specific symptoms such as abdominal pain, nausea, vomiting, diarrhea or constipation. The purpose of this review is to provide a focused comprehensive discussion on the presentation, pathophysiology, diagnostic evaluation and management of those diseases that arise from the gastrointestinal tract or other site that may cause gastrointestinal symptoms secondarily accompanied by flushing. This review is divided into two parts given the scope of conditions that cause flushing and affect the gastrointestinal tract: Part 1 covers neuroendocrine tumors (carcinoid, pheochromocytomas, vasoactive intestinal polypeptide, medullary carcinoma of the thyroid), polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS), and conditions involving mast cells and basophils; while Part 2 covers dumping syndrome, mesenteric traction syndrome, rosacea, hyperthyroidism and thyroid storm, anaphylaxis, panic disorders, paroxysmal extreme pain disorder, and food, alcohol and medications.