Recently developed radiopharmaceuticals for bacterial infection imaging.

BACKGROUND: Infection remains a major cause of morbidity and mortality, regardless of advances in antimicrobial therapy and improved knowledge of microorganisms. With the major global threat posed by antimicrobial resistance, fast and accurate diagnosis of infections, and the reliable identification of intractable infection, are becoming more crucial for effective treatment and the application of antibiotic stewardship. Molecular imaging with the use of nuclear medicine allows early detection and localisation of infection and inflammatory processes, as well as accurate monitoring of treatment response. There has been a continuous search for more specific radiopharmaceuticals to be utilised for infection imaging. This review summarises the most prominent discoveries in specifically bacterial infection imaging agents over the last five years, since 2019. MAIN BODY: Some promising new radiopharmaceuticals evaluated in patient studies are reported here, including radiolabelled bacterial siderophores like [68Ga]Ga-DFO-B, radiolabelled antimicrobial peptide/peptide fragments like [68Ga]Ga-NOTA-UBI29-41, and agents that target bacterial synthesis pathways (folic acid and peptidoglycan) like [11C]para-aminobenzoic acid and D-methyl-[11C]-methionine, with clinical trials underway for [18F]fluorodeoxy-sorbitol, as well as for 11C- and 18F-labelled trimethoprim. CONCLUSION: It is evident that a great deal of effort has gone into the development of new radiopharmaceuticals for infection imaging over the last few years, with remarkable progress in preclinical investigations. However, translation to clinical trials, and eventually clinical Nuclear Medicine practice, is apparently slow. It is the authors' opinion that a more structured and harmonised preclinical setting and well-designed clinical investigations are the key to reliably evaluate the true potential of the newly proposed infection imaging agents.

Radiation exposure of Staff handling 18Fluorine-Fluorodeoxyglucose in a new positron emission tomography/computed tomography centre.

Background: Positron emission tomography/computed tomography (PET/CT) is an imaging modality that combines images from high-energy gamma rays emitted by a positron emitting radiopharmaceutical and those from the CT component. The images are then used in the diagnosis of severe diseases. Procedures with PET radiopharmaceuticals introduce a risk of high occupational radiation exposure to staff handling them. 18Fluorine-Fluorodeoxyglucose ([18F]FDG) is the most commonly used PET radiopharmaceutical. Aim: To determine the radiation exposure of staff working at the PET/CT facility. Setting: Academic hospital in Gauteng. Methods: The study was quantitative and descriptive. The radiation exposure data of participants were collected using Polimaster®electronic pocket dosimeters, ring dosimeters and thermoluminescent dosimeters. The participants' workflow was tracked and the tasks that led to the highest radiation exposure were identified. Results: Radiopharmacists had 129 dispensing days with the resultant daily radiation exposure ranging between 0.01 µSv and 0.32 µSv. The radiographers' daily radiation exposure ranged between 7.08 µSv and 19.14 µSv. Radiographers received the highest radiation dose during radiopharmaceutical injection (average = 1.86 µSv). Conclusion: The study found that staff working at a new PET/CT facility in Gauteng were not at risk of radiation exposure above the accepted annual limits, which are 20 mSv per annum, averaged over 5 years, and with no more than 50 mSv in 1 year. Contribution: The findings revealed the need for continuous training in radiation protection measures for all staff working in the PET/CT facility.

89Zr-leukocyte labelling for cell trafficking: in vitro and preclinical investigations.

BACKGROUND: The non-invasive imaging of leukocyte trafficking to assess inflammatory areas and monitor immunotherapy is currently generating great interest. There is a need to develop more robust cell labelling and imaging approaches to track living cells. Positron emission tomography (PET), a highly sensitive molecular imaging technique, allows precise signals to be produced from radiolabelled moieties. Here, we developed a novel leukocyte labelling approach with the PET radioisotope zirconium-89 (89Zr, half-life of 78.4 h). Experiments were carried out using human leukocytes, freshly isolated from whole human blood. RESULTS: The 89Zr-leukocyte labelling efficiency ranged from 46 to 87% after 30-60 min. Radioactivity concentrations of labelled cells were up to 0.28 MBq/1 million cells. Systemically administered 89Zr-labelled leukocytes produced high-contrast murine PET images at 1 h-5 days post injection. Murine biodistribution data showed that cells primarily distributed to the lung, liver, and spleen at 1 h post injection, and are then gradually trafficked to liver and spleen over 5 days. Histological analysis demonstrated that exogenously 89Zr-labelled human leukocytes were present in the lung, liver, and spleen at 1 h post injection. However, intravenously injected free [89Zr]Zr4+ ion showed retention only in the bone with no radioactivity in the lung at 5 days post injection, which implied good stability of radiolabelled leukocytes in vivo. CONCLUSIONS: Our study presents a stable and generic radiolabelling technique to track leukocytes with PET imaging and shows great potential for further applications in inflammatory cell and other types of cell trafficking studies.

Iridoid Derivatives as Anticancer Agents: An Updated Review from 1970-2022.

The rise of cancer cases has coincided with the urgent need for the development of potent chemical entities and/or modification of existing commodities to improve their efficacy. Increasing evidence suggests that cancer remains one of the leading causes of death globally, with colon cancer cases alone likely to rise exponentially by 2030. The exponential rise in cancer prevalence is largely attributable to the growing change toward a sedentary lifestyle and modern diets, which include genetically modified foods. At present, the prominent treatments for cancer are chemotherapy, surgery, and radiation. Despite slowing cancer progression, these treatments are known to have devastating side effects that may deteriorate the health of the patient, thus, have a low risk-benefit ratio. In addition, many cancer drugs have low bioavailability, thereby limiting their therapeutic effects in cancer patients. Moreover, the drastic rise in the resistance of neoplastic cells to chemotherapeutic agents is rendering the use of some drugs ineffective, thereby signaling the need for more anticancer chemical entities. As a result, the use of natural derivatives as anticancer agents is gaining considerable attention. Iridoids have the potential to form conjugates with other anticancer, antidiabetic, antileishmanial, and antimalarial drugs, which synergistically have the potential to increase their effects. Published studies have identified the role of iridoids, which, if fully explored, may result in cheaper and less toxic alternative/adjuvant cancer drugs. The subject of this article is natural and synthetic iridoid derivatives and their potential therapeutic roles as anticancer agents.

Changes in levels of omega-O-acylceramides and related processing enzymes of sun-exposed and sun-protected facial stratum corneum in differently pigmented ethnic groups.

INTRODUCTION: We report on the differences in ceramide composition and levels of omega-O-acylceramide processing enzymes of sun-exposed and sun-protected facialstratum corneum (SC) among Albino African, Black African and Caucasian women living in South Africa. METHODS: Tape strippings were taken from the sun-exposed cheek and the sunprotected postauricular site (PA). In two subsets proteomic (n = 18) and lipidomic (n = 24) analysis were performed using mass-spectrometry-based shotgun platforms. RESULTS: No significant differences in total ceramide levels or ceramide subtypes were found between the Black African and Caucasian women in either the cheek or PA samples. Compared to the other two groups the levels of total ceramide as well as selected omega-O-acylceramide species were increased in Albino Africans. On the cheek, ceramide (CER) EOS, EOH along with CER AS were increased relative to the Caucasian women, while CER EOP and EOdS were elevated relative to the Black African women. Moreover, on the PA site CER EOP and EOdS were elevated compared with the Black African women and CER EOdS in Caucasians. Decreasesin masslevels of 12R-LOX and eLOX3 were observed on cheeks compared with the PA sites in all ethnic groups. On the PA sites 12R-LOX was particularly lower in the Albino Africans compared with the Black African and Caucasian women. On the cheeks mass levels of SDR9C7 was also lower in the Albino Africans. CONCLUSION: The mass levels of the ceramides were similar between Black African and Caucasian women. However, elevated total ceramides and excessively elevated selected omega-O-acylceramides were apparent in the Albino African women. The findings in the Albino African women were unexpected as these participants suffer from impaired skin barrier function. However, the elevated levels omega-O-acylceramides can contribute to barrier insufficiency by directly impacting SC lipid phase behaviour and/or secondly elevated omegaO-acylceramide levels may indicate a reduced attachment of ceramides to the corneocyte lipid envelope and reduced corneocyte maturation that can also impair the barrier. Indeed, differences in the mass levels of omega-O-acylceramide processing enzymes were observed for 12R-LOX and SDR9C7 for the Albino Africans. This indicates a corneocyte lipid scaffold disorder in this population.

INTRODUCTION: Nous décrivons les différences de composition en céramides et de niveaux des enzymes du métabolisme des oméga-O-acylcéramides du stratum corneum facial (SC) photo-exposé et photo-protégé chez des femmes Albinos Africaines, Noires Africaines et Caucasiennes vivant en Afrique du Sud. MÉTHODES: Les prélèvements ont été effectués sur la joue photo-exposée et sur le site post-auriculaire (PA) photo-protégé à l'aide de disques adhésifs. Dans deux sous-groupes, des analyses protéomiques (n = 18) et lipidomiques (n = 24) ont été réalisées à l'aide de plateformes de spectrométrie de masse non-ciblées. RÉSULTATS: Aucune différence significative de quantité globale de céramides ou dans les différentes classes de céramides n'a été observée entre les femmes Noires Africaines et les femmes Caucasiennes, quels que soient les échantillons (Joue ou de PA). Comparativement aux deux autres groupes, les quantités de céramides totales, ainsi que certaines espèces d'oméga-O-acylcéramides, étaient plus élevés chez les femmes Albinos Africaines. Sur la joue, les céramides (CER) EOS, EOH et CER AS étaient plus élevés que chez les femmes Caucasiennes, tandis que les CER EOP et EOdS étaient plus élevés que chez les femmes Noires Africaines. De plus, sur le site PA, les CER EOP et EOdS étaient plus élevés que chez les femmes Noires Africaines et les CER EOdS chez les Caucasiennes. Des diminutions des niveaux d'enzymes 12R-LOX et eLOX3 ont été observées sur les joues par rapport aux sites PA dans tous les groupes ethniques. Sur les sites PA, le niveau de 12RLOX était notablement plus faible chez les femmes Albinos Africaines comparativement aux femmes Noires Africaines et Caucasiennes. Sur les joues, le niveau de SDR9C7 était également plus faible chez les Albinos Africaines. CONCLUSION: La masse des céramides totaux était similaire entre les femmes Noires Africaines et Caucasiennes. Cependant, des niveaux élevés de céramides totaux et excessivement élevés des oméga-O-acylcéramides sélectionnés, ont été observés chez les femmes Albinos Africaines. Les résultats obtenus chez les femmes Albinos Africaines étaient surprenants car ces participantes souffrent d'une altération de la fonction de la barrière cutanée. Néanmoins, les niveaux élevés d'oméga-O-acylcéramides peuvent en premier lieu contribuer à l'insuffisance de la barrière en ayant un impact direct sur le comportement de la phase lipidique du SC et/ou, deuxièmement, peuvent indiquer une fixation réduite des céramides à l'enveloppe lipidique des cornéocytes et une maturation réduite des cornéocytes pouvant aussi altérer la barrière. En outre, des différences dans les niveaux d'expression des enzymes de transformation de l'oméga-O-acylcéramide ont été observées pour 12R-LOX et SDR9C7 chez les femmes Albinos Africaines. Ceci indique une désorganisation de l'échafaudage lipidique des cornéocytes dans cette population.

Beauty in Baobab: a pilot study of the safety and efficacy of Adansonia digitata seed oil

ABSTRACT Recently there has been a renewed impetus in the search for novel ingredients to be used in the cosmetic industry and Baobab (Adansonia digitata L., Malvaceae) seed oil has received high interest. In this study, a commercial Baobab seed oil sample was characterised (fatty acid content) using GCxGC-ToF-MS and a pilot study on the safety and efficacy of the seed oil was performed. The safety and efficacy of Baobab seed oil after topical application was determined using healthy adult female caucasian participants (n = 20). A 2× magnifying lamp was used for visual analysis, while for monitoring and evaluation of the irritancy level, transepidermal water loss (TEWL) and hydration level of the skin, Chromameter®, Aquaflux® and Corneometer® instruments, respectively, were used. In addition, Aquaflux® and Corneometer® instruments were used to assess occlusive effects. Thirteen methyl esters were identified using GCxGC-ToF-MS. The major fatty acids included 36.0% linoleic acid, 25.1% oleic acid and 28.8% palmitic acid with 10.1% constituting trace fatty acids. The irritancy of sodium lauryl sulphate (SLS) in the patch test differed significantly compared to both de-ionised water (p < 0.001) and Baobab seed oil (p < 0.001) but the difference between the irritancy of Baobab seed oil and de-ionised water was not significant (p = 0.850). The moisture efficacy test indicated a reduced TEWL (p = 0.048) and an improved capacitance moisture retention (p < 0.001) for all the test products (Baobab oil, liquid paraffin, Vaseline® intensive care lotion and Vaseline®). The occlusivity wipe-off test indicated an increased moisture hydration (p < 0.001) and decreased TEWL particularly when Baobab oil was applied. Baobab possesses hydrating, moisturising and occlusive properties when topically applied to the skin. Baobab seed oil could be a valuable functional ingredient for cosmeceutical applications.

Safety and efficacy of Sclerocarya birrea (A.Rich.) Hochst (Marula) oil: A clinical perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Sclerocarya birrea (A.Rich.) Hochst (Marula) nut oil is a popular ingredient in cosmetics such as skin lotions, lipsticks and foundations. The demand for this African oil increased tremendously such that in 2008 almost US$ 20 million was spent on Marula oil for cosmetic product manufacturing. The ethnobotanical literature states that the Zulu people in South Africa amongst others applied the oil to maintain a healthy skin. Scientific studies to support the traditional use as well as the inclusion of Marula oil in cosmetic products is lacking. This study evaluated the irritancy potential (safety), the moisturising and hydrating effects as well occlusivity properties (efficacy) of Marula oil after topical application. In addition, the Marula oil used in this study was comprehensively characterised using two-dimensional gas chromatography coupled to mass spectrometry. METHODS AND MATERIALS: Quantification of the fatty acid methyl esters (FAMEs) was done using a LECO Pegasus 4D GC × GC-MS. To determine the safety and efficacy of Marula oil healthy caucasian adult female volunteers (n = 20) who complied with the inclusion and exclusion criteria for the irritancy patch, moisture efficacy, hydrating and occlusivity tests were recruited for each study. A 2 × magnifying lamp (visual observation), Chromameter®, Aquaflux® and Corneometer® instruments were used to evaluate and monitor the irritancy level, skin barrier function, transepidermal water loss, hydrating and occlusive effects of topically applied Marula oil. RESULTS: The GC × GC-MS analysis identified several saturated as well as unsaturated fatty acids. Oleic acid was the major fatty acid constituting 69.0% of the oil followed by palmitic acid (15.3%), linoleic acid (9.2%), palmitoleic acid (4.1%) and stearic acid (1.5%). The clinical study revealed that Marula oil is non-irritant (p < 0.001), with moisturising and hydrating properties (p < 0.001) when applied to a lipid-dry (xerosis) skin. Additionally the oil exhibited occlusive effects (p < 0.001) when applied to normal skin. These findings may be linked to the absorption of the oil into the skin due to the high percentage of oleic acid and the presence of palmitic acid which are known to disturb the stratum corneum intercellular lipids. These fatty acids present in Marula oil are very similar to those present in the epidermis, and can be considered biomimetic. CONCLUSIONS: Marula oil rich in fatty acids exhibits moisturising, hydrating and occlusive properties. As the oil is non-irritating and provides a moisturising effect with moderate prevention of transepidermal water loss, average moisture retention properties and noteworthy occlusive effects, its inclusion in cosmetic products based on its traditional use may be justified depending on the application.

Evaluating the Photoprotective Effects of Ochre on Human Skin by In Vivo SPF Assessment: Implications for Human Evolution, Adaptation and Dispersal.

Archaeological indicators of cognitively modern behaviour become increasingly prevalent during the African Middle Stone Age (MSA). Although the exploitation of ochre is viewed as a key feature of the emergence of modern human behaviour, the uses to which ochre and ochre-based mixtures were put remain ambiguous. Here we present the results of an experimental study exploring the efficacy of ochre as a topical photoprotective compound. This is achieved through the in vivo calculation of the sun protection factor (SPF) values of ochre samples obtained from Ovahimba women (Kunene Region, Northern Namibia) and the Palaeozoic Bokkeveld Group deposits of the Cape Supergroup (Western Cape Province, South Africa). We employ visible spectroscopy, energy-dispersive X-ray fluorescence (ED-XRF), X-ray diffraction (XRD) and granulometric analyses to characterise ochre samples. The capacity of ochre to inhibit the susceptibility of humans to the harmful effects of exposure to ultraviolet radiation (UVR) is confirmed and the mechanisms implicated in the efficacy of ochre as a sunscreen identified. It is posited that the habitual application of ochre may have represented a crucial innovation for MSA humans by limiting the adverse effects of ultraviolet exposure. This may have facilitated the colonisation of geographic regions largely unfavourable to the constitutive skin colour of newly arriving populations.

Cosmetic and amino acid analysis of the effects of lye and no-lye relaxer treatment on adult black female South African hair.

Surveys indicate that many South African women use relaxers to straighten their hair for cosmetic reasons, which can damage the hair and scalp. The objective of this study was to assess the effects of treating hair with two types of relaxers: Product A (a lye relaxer, sodium hydroxide base) and Product B (a no-lye relaxer, guanidine hydroxide base). Five adult black female South African subjects were used for the study that was divided into two parts. The first part used a half-head study design in a clinical study in which the researcher and the subjects visually assessed various hair quality parameters before and after relaxer treatment. Product B was assessed to perform better (p = 0.032) than Product A in terms of hair straightening. The second part of the study involved hair amino acid analysis by reversed-phase high performance liquid chromatography. There was a decrease in the amount of cystine [Median (range) g/100 g hair] after treatment with both Product A [7.8 (2.5-9.9), p = 0.086] and Product B [4.0 (2.9-4.8), p = 0.005] compared to before treatment [9.1 (6.4-11.9)]; this decrease was greater (p = 0.085) for Product B. Reduction in cystine content was consistent with increased straightness. Product B (the no-lye relaxer) was found to be more effective and safer to use.

Chemical analysis and in vitro†UV-protection characteristics of clays traditionally used for sun protection in South Africa.

Clays have been used in southern Africa as photoprotectants by the indigenous people. Typically, two types of clay are used: one white in colour and the other red. In this work, the two clays were identified and characterized, and their in vitro SPF values measured. The clays afford a low SPF but offer broad-spectrum protection. No cutaneous side effects from the use of these clays are known. Further consideration should be given to the potential use of clays in sunscreen preparations.

Facial skin-lightening benefits of the tetrapeptide Pro-Lys-Glu-Lys on subjects with skin types V-VI living in South Africa.

BACKGROUND: Irregular skin pigmentation may be a substantial contributor to the signs of aging and to a person's lack of psychological well-being. Although a large number of skin-lightening agents are available, the opportunity exists to identify more efficacious agents, agents that target alternative biological mechanisms. AIMS: To provide clinical evidence of the skin-lightening effect of the tetrapeptide, Pro-Lys-Glu-Lys (PKEK), on subjects with skin types V-VI living in South Africa. METHODS: Pro-Lys-Glu-Lys was evaluated in a double-blind and vehicle-controlled clinical study using expert grading of digital images by comparing its effects in subjects with skin types V-VI suffering from facial melasma and postinflammatory hyperpigmentation. RESULTS: This study demonstrated the efficacy of PKEK on subjects with skin types V-VI. On comparing the two treatments, the skin-lightening peptide-containing formulation was significantly superior to the vehicle at 12 weeks on overall appearance (P < 0.05) and evenness of skin tone (P < 0.01). CONCLUSIONS: The tetrapeptide, PKEK, has proven skin-lightening benefits on skin discoloration from melasma and postinflammatory hyperpigmentation. These studies have been conducted on subjects with skin types V-VI living in South Africa, but we believe this technology to be suitable for all racial groups.