Multimodal Imaging and Phototherapy of Cancer and Bacterial Infection by Graphene and Related Nanocomposites.

The advancements in nanotechnology and nanomedicine are projected to solve many glitches in medicine, especially in the fields of cancer and infectious diseases, which are ranked in the top five most dangerous deadly diseases worldwide by the WHO. There is great concern to eradicate these problems with accurate diagnosis and therapies. Among many developed therapeutic models, near infra-red mediated phototherapy is a non-invasive technique used to invade many persistent tumors and bacterial infections with less inflammation compared with traditional therapeutic models such as radiation therapy, chemotherapy, and surgeries. Herein, we firstly summarize the up-to-date research on graphene phototheranostics for a better understanding of this field of research. We discuss the preparation and functionalization of graphene nanomaterials with various biocompatible components, such as metals, metal oxides, polymers, photosensitizers, and drugs, through covalent and noncovalent approaches. The multifunctional nanographene is used to diagnose the disease with confocal laser scanning microscopy, magnetic resonance imaging computed tomography, positron emission tomography, photoacoustic imaging, Raman, and ToF-SMIS to visualize inside the biological system for imaging-guided therapy are discussed. Further, treatment of disease by photothermal and photodynamic therapies against different cancers and bacterial infections are carefully conferred herein along with challenges and future perspectives.

Near-infrared chemiluminescent nanoprobes for deep imaging and synergistic photothermal-nitric-oxide therapy of bacterial infection.

Bacterial infection is the leading cause of many serious inflammation diseases threatening human health. Existing theranostic options for bacterial infection are always complicated and unsatisfactory. There is an increasing interest in developing a more effective theranostic approach for the treatment of infections. Herein, we report the development of a near-infrared (NIR) chemiluminescent (CL) nanoparticles ALPBs containing luminol, AIE dye (TTDC), PCPDTBT, and nitric oxide (NO) donor (BNN6), which could achieve a deep CL imaging-guided photothermal-NO gas therapy of bacterial infection. After intravenous injection, ALPBs could be largely accumulated in the infected site and then activated by oversecreted reactive oxygen species (ROS) to produce near-infrared chemiluminescence, which could precisely track infection-induced local inflammation. Under the guidance of imaging, synergistic photothermal-NO therapy was further performed by 808 nm laser irradiation, leading to active bacterial eradication and rapid recovery of infected tissues. The utility of ALPBs provides a powerful and controllable "all-in-one" platform for combating bacterial infection.

Photoacoustic Imaging-Trackable Magnetic Microswimmers for Pathogenic Bacterial Infection Treatment.

Micro/nanorobots have been extensively explored as a tetherless small-scale robotic biodevice to perform minimally invasive interventions in hard-to-reach regions. Despite the emergence of versatile micro/nanorobots in recent years, matched in vivo development remains challenging, limited by unsatisfactory integration of core functions. Herein, we report a polydopamine (PDA)-coated magnetic microswimmer consisting of a magnetized Spirulina (MSP) matrix and PDA surface. Apart from the properties of the existing MSP (e.g., robust propulsion, natural fluorescence, tailored biodegradation, and selective cytotoxicity), the introduced PDA coating enhances the photoacoustic (PA) signal and photothermal effect of the MSP, thus making PA image tracking and photothermal therapy possible. Meanwhile, the PDA's innate fluorescence quenching and diverse surface reactivity allows an off-on fluorescence diagnosis with fluorescence probes (e.g., coumarin 7). As a proof of concept, real-time image tracking (by PA imaging) and desired theranostic capabilities of PDA-MSP microswimmer swarms are demonstrated for the treatment of pathogenic bacterial infection. Our study suggests a feasible antibacterial microrobot for in vivo development and a facile yet versatile functionalization strategy of micro/nanorobots.

Bacteria-induced aggregation of bioorthogonal gold nanoparticles for SERS imaging and enhanced photothermal ablation of Gram-positive bacteria.

The challenge in antimicrobial photothermal therapy (PTT) is to develop strategies for decreasing the damage to cells and increasing the antibacterial efficiency. Herein, we report a novel theranostic strategy based on bacteria-induced gold nanoparticle (GNP) aggregation, in which GNPs in situ aggregated on the bacterial surface via specific targeting of vancomycin and bioorthogonal cycloaddition. Plasmonic coupling between adjacent GNPs exhibited a strong "hot spot" effect, enabling effective surface enhanced Raman scattering (SERS) imaging of bacterial pathogens. More importantly, in situ aggregation of GNPs showed strong NIR adsorption and high photothermal conversion, allowing enhanced photokilling activity against Gram-positive bacteria. In the absence of bacterial strains, GNPs were dispersed and showed a very low photothermal effect, minimizing the side effects towards surrounding healthy tissues. Given the above advantages, the bioorthogonal theranostic strategy developed in this study may find potential applications in treating bacterial infection and even multidrug-resistant bacteria.

Ciprofloxacin: from infection therapy to molecular imaging.

Diagnosis of deep-seated bacterial infection remains a serious medical challenge. The situation is becoming more severe with the increasing prevalence of bacteria that are resistant to multiple antibiotic classes. Early efforts to develop imaging agents for infection, such as technetium-99m (99mTc) labeled leukocytes, were encouraging, but they failed to differentiate between bacterial infection and sterile inflammation. Other diagnostic techniques, such as ultrasonography, magnetic resonance imaging, and computed tomography, also fail to distinguish between bacterial infection and sterile inflammation. In an attempt to bypass these problems, the potent, broad-spectrum antibiotic ciprofloxacin was labeled with 99mTc to image bacterial infection. Initial results were encouraging, but excitement declined when controversial results were reported. Subsequent radiolabeling of ciprofloxacin with 99mTc using tricarbonyl and nitrido core, fluorine and rhenium couldn't produce robust infection imaging agent and remained in discussion. The issue of developing a robust probe can be approached by reviewing the broad-spectrum activity of ciprofloxacin, labeling strategies, potential for imaging infection, and structure-activity (specificity) relationships. In this review we discuss ways to accelerate efforts to improve the specificity of ciprofloxacin-based imaging.

Ruthenium complexes/polypeptide self-assembled nanoparticles for identification of bacterial infection and targeted antibacterial research.

Bacterial infection has been a threat to human health, and so early diagnosis and treatment of bacterial infection is an urgent problem that needs to be solved. In this work, a multifunctional theranostic selenium nanoplatform (Se@PEP-Ru NPs) with early imaging diagnosis and efficient treatment of bacterial infections was designed and constructed. First, the antibacterial peptide UBI29-41 (PEP) was linked to functionalized Selenium nanoparticles (NPs), which enhanced the stability of the antimicrobial peptide and also caused the nanocomposites to specifically target bacterial infection. Ruthenium complexes with good antibacterial activity and fluorescence properties were then coated on to their outer layers. It was worth mentioning that, when the resulting nanoprobe was injected into mice by intravenous injection it was found to be sensitive to sites of bacterial infection for selective fluorescence imaging and targeted therapy. Thus, it can be used to distinguish between bacterial infection, inflammation, and tumor-induced tissue infection with high specificity. In the further antibacterial activity experiments, Ruthenium complexes showed synergistic antimicrobial activity with Se NPs, which indicated that the antibacterial activity of Se@PEP-Ru NPs was the strongest that could promote wound healing. Thus, Se@PEP-Ru NPs appears to be a promising antimicrobial with good biocompatibility, excellent selectivity, and potent antimicrobial activity.

Nuclear medicine imaging of bone infections.

Osteomyelitis is a broad group of infectious diseases that involve the bone and/or bone marrow. It can arise haematogenously, via extension from a contiguous infection, or by direct inoculation during surgery or trauma. The diagnosis is not always obvious and imaging tests are frequently performed as part of the diagnostic work-up. Commonly performed radionuclide tests include technetium-99m ((99m)Tc)-diphosphonate bone scintigraphy (bone), and gallium-67 ((67)Ga) and in vitro labelled leukocyte (white blood cell; WBC) imaging. Although they are useful, each of these tests has limitations. Bone scintigraphy is sensitive but not specific, especially when underlying osseous abnormalities are present. (67)Ga accumulates in tumour, trauma, and in aseptic inflammation; furthermore, there is typically an interval of 1-3 days between radiopharmaceutical injection of and imaging. Currently, this agent is used primarily for spinal infections. Except for the spine, WBC imaging is the nuclear medicine test of choice for diagnosing complicating osteomyelitis. The in vitro leukocyte labelling process requires skilled personnel, is laborious, and is not always available. Complementary marrow imaging is usually required to maximise accuracy. Not surprisingly, alternative radiopharmaceuticals are continuously being investigated. Radiolabelled anti-granulocyte antibodies and antibody fragments, investigated as in vivo leukocyte labelling agents, have their own limitations and are not widely available. (111)In-biotin is useful for diagnosing spinal infections. Radiolabelled synthetic fragments of ubiquicidin, a naturally occurring human antimicrobial peptide that targets bacteria, have shown promise as infection specific radiopharmaceuticals. 2-[(18)F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) with or without computed tomography (CT) is very useful in musculoskeletal infection. Sensitivities of more than 95% and specificities ranging from 75-99% have been reported in acute and subacute bone and soft-tissue infection. FDG is the radionuclide test of choice for spinal infection. It is sensitive, has a high negative predictive value, and can differentiate degenerative from infectious vertebral body end-plate abnormalities. Data on the accuracy of FDG for diagnosing diabetic pedal osteomyelitis and prosthetic joint infection are inconclusive and its role for these indications remains to be determined. Other PET radiopharmaceuticals that are under investigation as infection imaging agents include gallium-68 citrate ((68)Ga) and iodine-124 fialuridine ((124)I -FIAU).

Preclinical testing of radiopharmaceuticals for novel applications in HIV, bacterial and fungal infectious diseases.

Antibiotics, antifungal and antiviral medications have traditionally been used in the management of infections. Due to widespread emergence of resistance to antimicrobial medications, and their side effects, there is a growing need for alternative approaches for management of such conditions. Antibiotic resistant bacterial pathogens are on the rise. A cure has not been achieved for viral infections like AIDS, while fungal and parasitic infections are constant threats to the health of general public. The incidence of opportunistic infections in immunocompromised individuals like HIV patients, patients receiving high dose steroids, chemotherapy patients, and organ transplant recipients is on the rise. Radioimmunotherapy (RIT) has the potential to be a suitable and viable therapeutic modality in the arena of infection management. Provided the target-associated antigen is expressed by the target cells and minimally or not expressed by other tissues, selective targeting of radiation to target sites can be theoretically accomplished with relative sparing normal tissues from radiation exposure. In our laboratory we successfully demonstrated the effectiveness of RIT for treating infectious diseases. We targeted murine cryptococcosis with a mAb to the Cryptococcus neoformans capsular glucuronoxylomannan labeled with Bismuth-213 ((213)Bi) or Rhenium-188 ((188)Re). We subsequently extended the applicability of RIT for treating bacterial and viral infections. One of the advantages of using RIT to treat infections as opposed to cancer is that, in contrast to tumor cells, cells expressing microbial antigens are antigenically very different from host tissues and thus provide the potential for exquisite specificity and low cross-reactivity. Ever increasing incidence of infectious pathologies, exhaustion of antimicrobial possibilities and rising drug resistance calls for use of alternative and novel therapeutic options and we believe RIT is the need of the hour to combat these infections.

Akut exazerbierende primär chronische Osteomyelitis der Mandibula im Kindesalter.

Inflammation of bone is caused either by bacterial infection or occasionally by physical stimulus. Primary chronic osteomyelitis of mandibular bone is a chronic inflammation of an unknown cause. Pain, swelling, limited mouth opening, regional lymphadenopathy and hypaesthesia are clinical symptoms at initial presentation. Results of biopsy, computed tomography and scintigraphy reveal the diagnosis of a primary chronic osteomyelitis. Its management is long-term antibiotic therapy, hyperbaric oxygen and surgical therapy, even bisphophonate treatement may be a good option. The case report presents a primary progressive chronic osteomyelitis of the manibular bone of a ten year old boy. Clinical and radiological signs are discussed as well as diagnosis, management and follow-up.

Efficacy of indigenously developed single vial kit preparation of 99mTc-ciprofloxacin in the detection of bacterial infection: an Indian experience.

OBJECTIVE: To investigate the diagnostic efficacy of indigenously developed single vial kit preparation of Tc-ciprofloxacin (Diagnobact) for the detection of orthopedic infections. METHODS: Seventy-seven patients [25 with clinical suspicion of diabetic foot osteomyelitis (DFOM), 25 with orthopedic device-related infection (ODRI) and 27 with tubercular bone infection] underwent three-phase Tc-methylenediphosphonate bone scintigraphy followed by static Tc-ciprofloxacin imaging at 1, 4 and 24 h. Imaging (anterior and posterior views) was performed under a dual-head gamma-camera using a low-energy, high-resolution, parallel-hole collimator. The lesion-to-background ratio (LBR) of the radiotracer was calculated on the static isotime Tc-ciprofloxacin images using semiquantitative analysis. Scintigraphic (Diagnobact) results were compared with the histopathological and/or culture/PCR analysis as a gold standard. RESULTS: The mean LBR of the radiotracer (Tc-ciprofloxacin) in the positive scans (n=29; 16 ODRI, 13 DFOM) was > or =2.0 at 1 h postinjection and remained consistent till 24 h. In contrast, the mean LBR in the negative scans (n=21; 12 DFOM, nine ODRI) was < or =1.5 at 1 h and declined significantly (P<0.05) at 24 h. The observed trend in the mean LBR in positive (n=18) and negative (n=9) scans for tubercular osteomyelitis was identical to that seen in the nontubercular bacterial infections. CONCLUSION: The management protocol for patients with suspected bony infection may include a three-phase bone scan followed by Tc-ciprofloxacin scan. An LBR of > or =2.0 at 1 h that remained consistent till 24 h on Tc-ciprofloxacin scan is indicative of active bacterial infection. However, resistance to ciprofloxacin at the bacterial cell membrane may be a limitation of this technique.

[Using AELTIS-synchro-02 device in the therapy of chronic bacterial prostatitis].

The treatment of chronic bacterial prostatitis combined antibacterial drugs and physiotherapy (low-energy laser radiation, electrostimulation of the prostate). Treatment of chronic bacterial prostatitis with medication and complex two-channel bio-synchronized electrolaser therapy with application of the unit AELTIS-synchro-02 raises efficacy of treatment with chronic bacterial prostatitis due to combined effect of antibacterial drugs and bacteriostatic and immunomodulating actions of the physical factors applied. These normalize microcirculation in the region of the prostatic gland, improve a draining function of the prostatic ducts, allows achievement of good results in 88.2% patients.

[Clinical-laboratory study of the efficacy of combined drug Cifran CT in complex therapy of inflammatory periodontal disease].

Data on clinical and microbiological study on 40 patients showed sufficient efficacy of combined preparation Cifran CT used in combined therapy of inflammatory periodontal disease.

Physician specialty is associated with differences in the evaluation and management of acute bacterial rhinosinusitis.

BACKGROUND: Acute bacterial rhinosinusitis (ABRS) is a common illness that is routinely managed by physicians from several different specialties. However, the actual diagnostic and treatment preferences of physicians from these different specialties are not known. OBJECTIVE: To determine whether the radiographic evaluation and management of community-acquired ABRS differs according to medical specialty. DESIGN, SETTING, AND PARTICIPANTS: Randomized survey of 450 board-certified physicians in the United States from family medicine, general internal medicine, and otolaryngology. MAIN OUTCOME MEASURES: Responding physicians' use of diagnostic radiography as well as choice and duration of antimicrobial and adjunctive treatments of ABRS. RESULTS: Otolaryngologists were more likely to use supportive diagnostic radiography (P =.04). They were also more likely to treat patients with adjunctive therapy, such as topical decongestants (P =.01), guaifenesin (P =.01), and saline nasal irrigation (P =.01), in addition to antibiotics. Otolaryngologists prescribed more medications to treat patients with ABRS than primary care physicians (P =.01). There were no significant differences in diagnosis and management by family physicians and general internists. CONCLUSIONS: Otolaryngologists use more health care resources to diagnose and treat ABRS than primary care physicians despite an absence of evidence that such tests and treatments lead to better outcomes. Otolaryngologists typically treat a patient population with a higher prevalence of ABRS and frequently see referred patients with recurrent acute sinusitis and chronic rhinosinusitis, which may explain their tendency to treat patients more aggressively. Nevertheless, these survey results illustrate a lack of consensus within the medical community regarding the evaluation and management of community-acquired ABRS, suggesting that widely accepted evidence-based practice guidelines need to be developed.

Bacterial osteomyelitis in adults: evolving considerations in diagnosis and treatment.

Bacterial osteomyelitis causes substantial morbidity worldwide, despite continued progress toward understanding its pathophysiology and optimal management. The approach to osteomyelitis depends upon the route by which bacteria gained access to bone, bacterial virulence, local and systemic host immune factors, and patient age. While imaging studies and nonspecific blood tests may suggest the diagnosis, an invasive technique is generally required to identify the causative pathogens. Given the paucity of comparative clinical trials, antibacterial regimen selection has been largely guided by knowledge of the relative activities and pharmacokinetics of individual drugs, supported by data from animal models. Definitive therapy often requires a combined medical and surgical approach. Newer microvascular and distraction osteogenesis techniques and the use of laser doppler allow more complete surgical resection of infected material while maintaining function. Despite recent advances, many patients with osteomyelitis fail aggressive medical and surgical therapy. More accurate diagnostic methods, better ways to assess and monitor the effectiveness of therapy, and novel approaches to eradicate sequestered bacteria are needed.

Evaluation of cefixime in the treatment of bacterial maxillary sinusitis.

The efficacy and safety of cefixime, the first oral third-generation cephalosporin, were evaluated in a multicenter clinical trial involving 118 adult patients with acute sinusitis or acute exacerbations of chronic sinusitis. Patients received a single daily dose of 400 mg of cefixime for a mean duration of 10 days; 106 patients completed a course of therapy. Clinical cure and improvement were achieved in 90% of these patients (61% cured and 29% improved). Among the patients evaluated again 2 weeks after therapy, 91% had a sustained clinical cure or improvement. Sinus exudate specimens were obtained from all patients by transantral puncture before therapy. Pathogens were isolated from 76 patients (66%), the most common pathogens being Haemophilus influenzae, alpha-hemolytic streptococci, and Streptococcus pneumoniae. Eighty-six percent of pathogens were presumed eradicated. Three patients discontinued therapy because of side effects. The most frequently reported adverse effects were gastrointestinal, with 20% of patients reporting diarrhea. Cefixime was effective in the treatment of bacterial sinus infections in adults and was well tolerated.

Non-traumatic brain abscess.

Between 1953 and 1989 eighty cases of non-traumatic brain abscess were treated in our department. We have re-examined the clinical and neuroradiological features of this pathological process and present our therapeutic approach and results. We believe that the optimal treatment for brain abscess consists of surgical removal. The prognosis for these lesions has undergone a marked improvement over the last two decades in response to neuroradiological, microbiological and surgical advances. The most influential prognostic factor seems to be preoperative clinical status.

[Hyperbaric oxygen therapy of anaerobic brain abscesses following tonsillectomy]. / Die hyperbare Sauerstofftherapie bei anaeroben Hirnabszessen nach Tonsillektomie.

This study describes the clinical course of a 31 year old woman who developed multiple anaerobic brain abscesses six days after tonsillectomy, followed by hemoparesis and dysarthria. In spite of craniotomy, repeated punctures and drainage of pus and high dose local and systemic antibiotics, there was an obvious deterioration in the patient's condition. Hyperbaric oxygen therapy was tried as a last resort. The patient improved quickly, and six months after the tonsillectomy seems to be neurologically symptomfree.