Efficacy and Possible Mechanism(s) of Action of Gallium Tetraphenylporphyrin Nanoparticles against HIV-TB Coinfection in an In Vitro Granuloma Structure Model.

Coinfection of Mycobacterium tuberculosis (Mtb) and human immunodeficiency virus-1 (HIV) is a significant public health concern. Treatment is challenging due to prolonged duration of therapy and drug interactions between antiretroviral therapy (ART) and anti-TB drugs. Noniron gallium meso-tetraphenyl porphyrin (GaTP), a heme mimetic, has shown broad antimicrobial activity. Here, we investigated the efficacy of nanoparticle encapsulating GaTP (GaNP) for the treatment of HIV and Mtb coinfection or single infection in in vitro granuloma structures. GaNP significantly reduced viable Mtb within primary human in vitro granuloma structures infected with Mtb H37Rv-lux and significantly reduced levels of HIV in CD4+ T cells infected with the virus axenically. Similarly, GaNP exhibited significant antimicrobial activity against HIV/Mtb-coinfected granuloma structures created in vitro, which contain the primary immune cells seen in human TB granulomas, including CD4+ T cells and macrophages, as assessed by a luciferase assay for Mtb and p24 ELISA for HIV detection. Furthermore, mechanistic studies revealed that GaTP increases the level of reactive oxygen species and inhibits catalase in Mtb. A significant increase in Mtb nitrate reductase activity was also observed when Mtb was incubated with GaTP and sodium nitrate. Overall, increased oxidative stress and nitrite levels induced by GaTP are consistent with the possibility that GaTP inhibits Mtb aerobic respiration, which leads to incomplete O2 reduction and a shift to respiration using exogenous NO3. These cumulative data continue to support the potential for developing the noniron heme analog GaTP and its nanoparticle GaNP as new therapeutic approaches for the treatment of HIV/Mtb coinfection.

Scar Tissue Catheter Tip Occlusion From an Intrathecal Baclofen Delivery: A Case Report and Review of the Literature.

Intrathecal morphine is associated with the complication of catheter tip granuloma which causes symptoms of decreased pain control, increased required dose, and neurological deficit. Catheter tip granulomas from intrathecal baclofen are thought to never occur because of the mechanism by which intrathecal morphine causes granulomas. We present a case of an intrathecal baclofen induced scarring of a catheter tip with clinical characteristics similar to some symptoms of granuloma. A 66-year-old woman with multiple sclerosis induced spasticity was partially controlled with intrathecal baclofen delivery at an extremely high dose of 1638 micrograms per day. She presented in the hospital with symptoms of withdrawal from intrathecal baclofen and required an emergency revision of her baclofen pump. Replacement of the catheter demonstrated complete occlusion of the catheter tip by scar tissue. Following surgery, her spasticity was well-controlled at the much lower dose of 200 micrograms per day. Intrathecal baclofen delivery can cause catheter tip scarring which causes some symptoms similar to catheter tip granuloma. Early recognition of these signs of catheter tip occlusion could help prevent progression to withdrawal.

Schistosomicidal Effects of Moringa oleifera Seed Oil Extract on Schistosoma mansoni-Infected Mice.

Schistosomiasis causes severe hepatic fibrosis, making it a global health issue. Moringa oleifera seed oil extract, which had antiparasitic, anti-inflammatory and antioxidant effects, was investigated as an alternative treatment. The 50 mice were divided into control, infected, praziquantel-treated, M. oleifera seed oil extract-treated and combined treatment groups. These treatments were examined for their effects on egg granulomas, hepatic enzymes, total protein, albumin, antioxidant enzymes and pro-inflammatory cytokines. M. oleifera seed oil and/or PZQ significantly reduced egg numbers, granuloma size and liver histopathology. M. oleifera seed oil reduced hepatic enzyme activity, increased total protein and albumin, and increased antioxidant enzyme activity while decreasing malondialdehyde. M. oleifera seed oil reduced the levels of pro-inflammatory cytokines. M. oleifera seed oil may treat schistosomiasis instead of PZQ due to its antifibrotic, immunomodulatory and schistosomicidal properties.

[Lessons on reactions to aesthetic fillers]. / Leçons sur les réactions aux produits de comblement à visée esthétique.

Any product injected to fill wrinkles can behave like a foreign body and cause unsightly granulomatous reactions. The subject is constantly evolving, subject to the vagaries of the market. Hyaluronic acid is the most injected product because it is resorbable and probably the least "toxic". In the event of sarcoidosis or an immune disorder, and in the event of vaccination against Covid, granulomas can develop even after very old injections.

Reactivation of Epstein-Barr virus by n-butyric acid from Pseudoramibacter alactolyticus induces inflammatory cytokines in periapical granulomas.

OBJECTIVES: This study investigates whether latent Epstein-Barr virus (EBV) can be reactivated by n-butyric acid from Pseudoramibacter alactolyticus, and if such reactivation induces expression of interleukin (IL)-1ß and IL-6 in periapical granulomas. METHODS: We analyzed periapical granulomas and healthy gingival tissues to detect the presence of EBV and P. alactolyticus. The concentration of n-butyric acid in P. alactolyticus culture supernatants was measured. BZLF-1 luciferase assays were conducted with or without these supernatants. Immunohistochemical detection of ZEBRA-, IL-1ß-, and IL-6-expressing cells was performed in the tissue samples. Additionally, mRNA expression levels of BZLF-1, IL-1ß, and IL-6 were quantified and statistically analyzed for correlation. The expression of these mRNAs was also measured in Daudi cells treated with or without the culture supernatants. RESULTS: Both EBV and P. alactolyticus were detected in periapical granulomas, but not in healthy tissues. The concentration of n-butyric acid in the culture supernatants was ∼3.58 mmol/L. BZLF-1 luciferase activity in the presence of the culture supernatants was comparable to that of commercially available butyric acid, whereas no activity was detected without the supernatants. Cells expressing ZEBRA co-expressed IL-1ß and IL-6. The mRNA levels of BZLF-1, IL-1ß, and IL-6 in periapical granulomas were correlated with the number of EBV DNA copies. Daudi cells treated with the culture supernatants expressed BZLF-1, IL-1ß, and IL-6 mRNA, while those without the supernatants did not. CONCLUSIONS: The study concludes that EBV can be reactivated by n-butyric acid produced by P. alactolyticus, leading to the induction of IL-1ß and IL-6 expression in periapical granulomas.

The New Frontier of JAK Inhibitors: Significant Therapeutic Response to Tofacitinib in a Patient With Granulomatous Reaction to Filler in the Buttocks.

BACKGROUND: Recent research has demonstrated that Janus Kinase (JAK) inhibitors can be effective in treating refractory granulomatous diseases. CASE PRESENTATION: We report the case of a 50-year-old woman who developed a granulomatous reaction following a filler injection in her buttocks. MANAGEMENT: The patient was treated with tofacitinib, and after 1 year of therapy, the stiffness and swelling resolved without any side effects. CONCLUSION: Tofacitinib appears to be a viable option for the treatment of granulomatous reactions to fillers.

Primary Sclerosing Cholangitis and Crohn's Disease: A Rare Association.

Inflammatory bowel disease (IBD) and primary sclerosing cholangitis (PSC) are closely associated disease entities that, when present in combination, create a phenotypically different summative disease referred to as PSC-IBD. The hallmark of Crohn's disease is persistent inflammation that can affect any part of the gastrointestinal system, from the mouth to the anus, although the terminal ileum and proximal colon are most frequently affected. Crohn's disease can sporadically impact the duodenum and stomach. Here, we present the case of a 12-year-old child who presented with per rectal bleed, hematemesis, and persistent elevated transaminasemia. A biopsy revealed micro-granulomas from the stomach's antrum and colonic mucosa, as well as focally exacerbated colitis. For a prolonged increased cholestatic pattern of liver enzymes, we performed an autoimmune panel and magnetic retrograde cholangiopancreatography, which revealed PSC. The patient was started on steroids and immunosuppressants.

Sarcoidosis with a Necrotizing Sarcoid Granulomatosis Pattern Presenting as Persistent Low-Grade Fever: A Case Report.

Necrotizing sarcoid granulomatosis (NSG), now referred to as "sarcoidosis with NSG pattern," is an uncommon variant of sarcoidosis. NSG is characterized by a trio of features: sarcoid granulomas, vasculitis, and extensive areas of necrosis. Symptoms can include cough, fever, chest pain, and dyspnea, typically presenting as either solitary or multiple lung nodules or masses. In this report, we describe a case of NSG accompanied by a persistent low-grade fever. Unlike the dominant presentation of NSG with single or multiple nodules, our case demonstrated diffuse micronodules with combined perilymphatic and random distribution on CT. Histological examination revealed widespread necrotizing granulomas surrounded by anthracotic pigmentation, alongside necrosis and vasculitis, diverging from the classic presentation of sarcoidosis. The diagnosis of NSG was established through a multidisciplinary discussion. The patient was administered oral prednisolone that led to noticeable clinical and radiological improvement within three months.

Radiotherapy Combined With Zoledronic Acid for Fibrous Dysplasia With a Central Giant Cell Granuloma: A Case Report.

BACKGROUND: Giant cell reparative granulomas are nonneoplastic, benign lesions that can expand and dissolve bone. Fibrous dysplasia is a benign condition in which normal bone tissue is replaced by abnormally proliferating immature reticular bone and fibrous tissue. The combination of giant cell reparative granuloma and fibrous dysplasia is extremely rare and can pose diagnostic and therapeutic challenges because of the complexity of clinical presentation. CASE PRESENTATION: We here present a patient who had a combination of fibrous dysplasia of bone and a giant cell reparative granuloma. An elderly male was admitted to the hospital with a blood-streaked nasal discharge, blurry vision in his right eye, and an enlarged mass under the chin. A CT scan revealed that the lesion had infiltrated the head and face extensively, including the right maxillary sinus, sieve sinus, and the right nasal cavity, contraindicating surgery. The patient received a total dose of 30 Gy of 6 MV x-ray radiotherapy delivered through helical tomotherapy over 15 sessions, with a single dose of 2 Gy being administered five times a week. Concurrently, The dose is 4 mg of zoledronic acid administered intravenously once every 21 days. After treatment, the patient's nasal congestion was significantly relieved, the vision of the right eye improved, and the mandibular lesion was significantly reduced. CONCLUSIONS: Treatment with radiotherapy combined with zoledronic acid for our patient's inoperable osteolytic giant cell reparative granuloma adjacent to vital nerves and blood vessels was extremely effective and safe. This case report provides a reference for the management of this rare combination.

Pulmonary Hyalinizing Granuloma: Case Report and Discussion of Diagnostic Challenges and Terminology.

Pulmonary hyalinizing granuloma (PHG) is a rare, benign condition characterized by slow-growing pulmonary nodules, often mimicking malignant lesions radiologically. Its pathogenesis is unclear but is thought to result from an exaggerated immune response to persistent antigenic stimuli. This report presents a case of a 71-year-old male with PHG, incidentally detected during imaging for acute appendicitis. Diagnostic challenges arose due to the radiological resemblance to metastatic disease, and inadequate biopsy samples. Surgical resection revealed fibrocollagenous nodules with perivascular inflammatory infiltrates. Immunohistochemistry and special stains excluded malignancy and infection. The clinical course of PHG is typically benign, with surgery being the treatment of choice for solitary lesions. However, the current terminology may be misleading, as the lesions are not true granulomas but rather fibrosing lesions. Further research is needed to clarify the underlying pathophysiology and improve diagnostic accuracy.

Routine Histopathology of Tonsillectomy Specimens, Is It Necessary? A Prospective Observational Study.

Routine histopathology of tonsillectomy specimens is not standard practice due to cost and resource constraints. This study aimed to evaluate the prevalence of abnormal histopathologies in tonsillectomy specimens to determine the necessity of routine histopathology. A prospective observational study was conducted from January 2014 to August 2016 at a general tertiary care center after approval of Institutional Ethics Committee (IEC). Patients scheduled for tonsillectomy surgery as per the AAOHNS 2011 criteria were included in the study. All tonsillectomy specimens were sent for histopathology, and abnormal findings were documented. Statistical analysis was performed. A total of 111 patients were enrolled in this study, and 222 tonsillectomy specimens were analyzed. The most common finding was chronic tonsillitis, which justified the selection criteria in 91.89% of patients. Two patients with chronic tonsillitis were also found to have actinomycosis present on the surface without parenchymal tissue reaction. Abnormal histopathological findings were observed in 9 (8.10%) of patients, leading to further investigations or treatment in 8 cases. These abnormalities included chronic granuloma, non-Hodgkin's lymphoma, early squamous cell carcinoma, and one choristoma. Tonsillar asymmetry, recent onset of symptoms and older age were found to be significantly correlated with abnormal histopathology and malignancy. Routine histopathology in tonsillectomy specimens helps to identify important findings that may require additional treatment. Based on the study we strongly recommend routine histopathology of tonsillectomy specimen. When significant cost constraints exist, risk-based approach can be adopted. Factors such as older age, asymmetry of tonsils, referred otalgia, duration of symptoms (recent onset) and a history of addiction should be considered for proceeding with histopathology. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-024-04888-1.

Orbital Cholesterol Granuloma : A Rare Case Report.

Cholesterol Granuloma is a rare lesion which occurs at locations like ear, peritoneum, lungs, breast etc. and formed due to interaction of Cholesterol and living tissue. But Cholesterol Granuloma occurring in the orbit is a very rare entity and so we authors present a case of Cholesterol Granuloma of the orbit.

A Novel Case of Paediatric Petrous Apex Cholesterol Granuloma.

The petrous apex is medial most part of temporal bone, which is surrounded by vital structures. Cholesterol granuloma is the most common benign lesion of the petrous apex. Symptoms are related to mass effect and/or direct involvement of closely adjacent vital structures. The lesions can be manged either by open surgery via craniotomy or through the newer endoscopic approach. Case report and review of the literature concerning cholesterol granulomas of the petrous apex and their management. The lesion was approached endoscopically trans nasal and trans sphenoid and cholesterol granuloma was excised and marsupialised. Post operative patient recovery was uneventful. Endonasal Endoscopic approach has significantly lower complication rate when compared to open approaches. Petrous apex lesions are rare and need a multidisciplinary team approach for optimal management. By endoscopic approach one can remove lesion or marsupialize the sac with natural drainage into sinus and result in better prognosis and minimal chance of recurrence. Endonasal procedure has also lower complication rates and shorter median follow-up than open approaches.

Silicone granuloma with intact breast implants: A case report.

Silicone granuloma formation is a potential complication of silicone implant rupture. Breast magnetic resonance imaging (MRI) is a useful diagnostic tool to assess implant integrity and complications; however, there can be overlap in the enhancement pattern of silicone granuloma and malignancy. We present the case of an 85 year old with suspicious axillary masses on clinical exam for which MRI was recommended. MRI demonstrated enhancing masses in the right axilla that were suspicious for malignancy and biopsy was ultimately performed. This case discusses the use of inversion recovery sequences on MRI, as well as ultrasound, to differentiate malignancy from silicone granuloma formation to prevent unnecessary biopsies.

Cholesterol Granuloma of the Lower Lip: Report of a Rare Case.

Cholesterol granuloma is the result of foreign body type response to the deposition of cholesterol crystals in the tissues. It is usually associated with chronic middle ear diseases and the middle ear and mastoid antrum are the most common location for this lesion. Histopathological findings are accumulation of cholesterol clefts, ghost cells, chronic inflammatory cells, and giant cells in a fibrous granulation tissue. Cases of cholesterol granuloma have been recently reported in the jaws but still they are few in the literature of dentistry. This article presents a unique case of cholesterol granuloma occurring in the lower lip secondary to a history of trauma.

Combined endovascular therapy and surgery for central giant cell granuloma in the temporal bone: A case report.

Background: Central giant cell granuloma (CGCG) is an uncommon, benign intraosseous lesion that most frequently occurs in the mandible and maxilla. Case Description: A 31-year-old female with a medical history of Kawasaki disease presented to our hospital complaining of a clogged right ear. Head computed tomography revealed a mass in the squamous part of the right temporal bone, with osteolytic changes and invasion of the external auditory canal, middle ear, temporomandibular joint, and mastoid air cells. Enhanced magnetic resonance imaging (MRI) showed a strong signal in the intraosseous lesion. Digital subtraction angiography revealed tumor staining from multiple feeders, including the middle meningeal, posterior deep temporal, and posterior auricular arteries. Preoperative feeder embolization using a detachable coil and Embosphere Microspheres were performed for the middle meningeal artery under general anesthesia. After the endovascular treatment, we operated on the temporal bone lesion. Postoperative enhanced MRI showed subtotal resection and residual tumor near the external auditory canal, which was left in place to prevent opening the external auditory canal. The histopathological examination showed proliferation of mononuclear cells intermingled with osteoclast-like multinucleated giant cells. A diagnosis of CGCG was made. The postoperative course was uncomplicated, and the patient was discharged on day 10 of hospitalization. Conclusion: We reported a rare case of CGCG in the temporal bone, managed by endovascular therapy and surgical resection. This combination therapy resulted in subtotal resection, preserving surrounding normal structures, such as the external auditory canal and tympanic cavity.

Neuroendocrine tumor mimicking a recalcitrant vocal fold granuloma: Appearances can be deceiving.

Posterior glottic lesions resembling granulomas unresponsive to conservative treatment should raise suspicion of a neoplastic condition. Although surgery is rarely recommended for arytenoid granulomas due to their high recurrence rate, histological evaluation is mandatory in cases of uncertain diagnosis. Clinicians should be aware that, although very rare, a laryngeal neuroendocrine tumor occurring in the posterior glottis can mimic the appearance of an idiopathic granuloma, presenting a diagnostic challenge.

Retroperitoneal granuloma in a cat caused by Nocardia brasiliensis resulting in bilateral ureteral entrapment and unilateral hydronephrosis.

Nocardia infections in cats most commonly present as subcutaneous wounds, or less commonly, as pneumonia, purulent pleurisy and disseminated disease. Abdominal involvement is rarely reported, and to date, localised retroperitoneal infection has only been reported in people. This report describes a five-year-old domestic shorthair cat living in Canberra, Australia, that presented with a two-month history of pyrexia and inappetence progressing to anorexia. Ultrasonography showed a large retroperitoneal mass incorporating both ureters. Euthanasia was elected because of the guarded prognosis. Necropsy examination revealed the mass to be comprised of extensive pyogranulomatous inflammation with fibrosis, Splendore-Hoeppli phenomenon and filamentous Gram-positive bacteria. Culture and MALDI-TOF mass spectrometry identified the causative agent as Nocardia brasiliensis. N. brasiliensis is commonly diagnosed as a cause of cutaneous nocardiosis in Australian human patients, but to date has only been reported in one cat from the United States and one dog from Australia. A treatment approach that might have been used in such a case is provided even though the cat's owners elected not to proceed with surgical intervention.